- 1Department of Pain Management and Research, Oslo University Hospital, University of Oslo, Oslo, Norway
- 2Department of Pain Management and Research, Oslo University Hospital, Oslo, Norway
Chronic widespread pain (CWP) is one of the most difficult pain conditions to treat due to an unknown etiology and a lack of innovative treatment design and effectiveness. Based upon preliminary findings within the fields of motivational psychology, integrative neuroscience, diaphragmatic breathing, and vagal nerve stimulation, we propose a new treatment intervention, motivational non-directive (ND) resonance breathing, as a means of reducing pain and suffering in patients with CWP. Motivational ND resonance breathing provides patients with a noninvasive means of potentially modulating five psychophysiological mechanisms imperative for endogenously treating pain and increasing overall quality of life.
Introduction and Background
Chronic widespread pain (CWP), including fibromyalgia syndrome (FMS), is a particular type of chronic primary pain where biological causalities may or may not be present and can not be identified as either musculoskeletal or neuropathic pain (Treede et al., 2015). CWP is a multifactorial pain condition characterized by prolonged pain that lasts for 3 months or more in multiple regions of the body. It is often associated with significant psychophysiological distress in the form of anxiety, anger, frustration, depression, insomnia, and social isolation (Maletic and Raison, 2009; Mansfield et al., 2017; World Health Organization, 2018). CWP is estimated to have a global prevalence of about one in every ten adults (Mansfield et al., 2016; Andrews et al., 2017) with a societal cost more than that of cancer and diabetes combined (Vos et al., 2013). Among all of the chronic pain conditions today, CWP is one of the most difficult to treat and manage (Lee et al., 2014).
Many of the symptoms associated with CWP overlap with those of functional somatic syndromes (FSS) (Henningsen et al., 2007) and medically unexplained symptoms (MUS) (Konnopka et al., 2012) where pathologically unexplainable patterns of persistent bodily complaints are present, some of which include pain in various locations, functional disturbances in different organ systems, and complaints centering around physical exhaustion and mental fatigue (Loeser and Melzack, 1999). Currently available treatments for FSS or MUS conditions provide modest improvements in pain and minimal improvements in both physical and emotional functioning (Turk et al., 2011). The difficulty to manage CWP in particular may be due to an unknown etiology (Sommer et al., 2008), an unstandardized definition (Butler et al., 2016), and a lack of both mainstream and alternative treatment modalities that are specifically designed to meet the psychophysiological profile of those suffering from it (Bee et al., 2016). General practitioners still have difficulty recognizing CWP and FMS as a valid diagnosis and often have limited awareness of diagnostic criteria and clinical models that may describe its psychosomatic interface (Mansfield et al., 2017).
Interdisciplinary theories which include the neurovisceral integration model (Thayer, 2007, 2009), the polyvagal theory (Porges, 2009; Kolacz and Porges, 2018), the biological behavioral model (Grossman and Taylor, 2007), the resonance frequency (RF) model (Lehrer, 2013), and the psychophysiological coherence model (McCraty and Childre, 2010) have all proposed that vagal tone (i.e., parasympathetic activity) is an arbiter for nurturing both psychological and physiological wellbeing. The neurovisceral integration model states that high vagal tone leads to better cognitive and emotional functioning as well as health regulation (Thayer, 2009). The polyvagal theory states that high vagal tone also leads to better social functioning (Kolacz and Porges, 2018). The biological behavioral model (Grossman and Taylor, 2007) understands vagal tone as a mediator and regulator of energy exchange through the synchronization of respiratory and cardiovascular processes during metabolic and behavioral changes. This model understands high vagal tone as a means of adaptation. In order to increase vagal tone, the RF breathing model was put forth which states that slow paced breathing at RF can increase vagal tone. Lastly, the psychophysiological coherence model (McCraty and Childre, 2010) takes it one step further by postulating that slow-paced breathing practiced with positive emotions can increase personal, social, and global health. Even though these theories share a common notion that vagal tone may be an important factor to consider when optimizing psychophysiological health, they lack a formalized means of methodologically applying the theory to practice within the field of CWP research and management.
Our unified theoretical approach herein referred to as the motivational nondirective resonance model attempts to bridge the aforementioned theories and describe a mechanism-based interventional approach, motivational non-directive (ND) resonance breathing, for treating CWP. To our knowledge, we are the first to propose such a unified theory and describe how it can be applied and tested as an innovative treatment for CWP. Interventions which have been previously developed in order to apply these theoretical findings to the development and delivery of new pain treatments have failed to sufficiently treat CWP.
None of the most commonly used pharmacological, psychological, medical, or surgical treatments are, by themselves, sufficiently able to remove pain or to significantly enhance physical and emotional functioning for patients suffering from CWP (Turk et al., 2011). However, primary care physicians continue to treat persistent pain conditions with chronic opioid therapy (Turner et al., 2016) despite the fact that opioids generally fail to alleviate pain intensity and function (Sullivan et al., 2008; Boudreau et al., 2009; Chou et al., 2015) and cause a myriad of adverse side effects (Ivanova et al., 2013; National Academies of Sciences Engineering and Medicine, 2017). This may be a reason as to why nearly half of those diagnosed with CWP/FMS still receive inadequate pain relief and often report partial or whole work incapacity (Breivik et al., 2006), increased sick-leave, poor quality of life and health (Gerdle et al., 2008; Mayer T.G. et al., 2008), and continue to suffer from a wide variety of psycho-social issues (Järemo et al., 2017).
Non-pharmacological treatments for FSS and MUS that involve the active participation of patients, such as exercise and psychotherapy, have been shown to be more effective than treatments which only involve passive physical measures (i.e., injections and operations) (Henningsen et al., 2007). Therefore, many patients decide to seek psycho- behavioral treatment plans that include adjunctive therapy or alternatives to medication (Chiesa and Serretti, 2011). A complementary and alternative medicine (CAM) survey report (Barnes et al., 2008) found that 4 out of 10 United States adults had used CAM therapy in the past 12 months. One of the most commonly used CAM therapies is deep breathing exercises for treating back pain, neck pain, and joint pain — all common symptoms inherent in those diagnosed with CWP (Barnes et al., 2008; Häuser et al., 2017). However, treatment modalities such as cognitive behavioral therapy, acceptance and commitment therapy, and mindfulness-based therapies — all of which commonly employ training modalities in intra and interpersonal psychology, deep breathing, positive affect, and executive control — have overall weak to moderate effect sizes for treating CWP when compared to treatment as usual, passive controls, and/or educational support groups (Morley et al., 1999; Hofmann and Asmundson, 2008).
In particular, research on mindfulness-based meditation interventions show contradictory findings (Farias et al., 2016), differences in conceptualization and practice (Chiesa and Malinowski, 2011), positive report biases (Coronado-Montoya et al., 2016), and only small to moderate effect sizes for treating pain in clinical populations (Veehof et al., 2011; Williams et al., 2012). Due to these findings, CWP continues to pose a tremendous burden on society and individuals (Hilton et al., 2016) who are searching for effective and integrative means of treatment. The overall inadequacy of mainstream and alternative treatments illustrates the necessity to develop innovative approaches for safely and effectively treating the specific psychophysiological framework of CWP. One promising avenue for treating CWP may be through the manipulation of respiratory mechanics.
Subsequent data shows a strong bidirectional relationship between pain and respiration (Perri and Halford, 2004; Smith et al., 2006; Jafari et al., 2017). Pain can cause faulty respiration (such as hyperventilation and breath-holding) which has a stronger association with chronic low back pain than obesity and physical activity (Borgbjerg et al., 1996; Nishino et al., 1999; Kato et al., 2001; Smith et al., 2006). Clinical studies demonstrate that deep breathing techniques may have positive effects for treating acute pain conditions (Jafari et al., 2017). However, the positive analgesic effects deep breathing may have on some acute pain conditions has failed to be established for CP conditions such as CWP. Experimental evidence elucidating the underlying psychophysiological mechanisms of how deep breathing may be used to treat CWP is lacking and often inconsistent (Jafari et al., 2017).
Due to the strong bidirectional relationship between pain and respiration, a recent systematic review (Jafari et al., 2017) called for future research to identify the autonomic and cardiovascular mediators that link respiration and pain; identify the physiological (i.e., respiratory) mechanisms needed to reduce pain; identify the central mechanisms responsible for producing respiratory hypoalgesia; and identify the psychological (i.e., behavioral) mechanisms needed to reduce pain.
In this paper, we propose that the autonomic and cardiovascular mediators that link respiration and CWP are baroreceptor sensitivity (BRS) and heart rate variability (HRV); the physiological mechanism needed to reduce pain in those with CWP is diaphragmatic breathing (DB) (i.e., RF breathing); the central mechanism responsible for producing respiratory hypoalgesia is vagus nerve stimulation; and the cognitive and affective psychological mechanisms needed to reduce pain in those with CWP is ND attention and motivation.
We believe that DB practiced at one’s RF has the potential to increase HRV and BRS by stimulating the vagal nerve in those suffering from CWP. Indeed, stimulation of the vagus nerve targets several pathophysiological factors associated with CWP. If diaphragmatic RF breathing is practiced with a ND quality of attention, we believe that this may be the ideal means of modulating specific brain activity (i.e., the default mode network) and thus remodel the relationship between CWP and emotion. Furthermore, motivating CWP patients to practice ND diaphragmatic RF breathing everyday while increasing their positive treatment expectations may aid in targeting the immune-mediated parameter of CWP. We hypothesize that motivational ND resonance breathing (MNRB) is a potential psychophysiological intervention for endogenously treating pain intensity and disability in those who suffer from CWP.
Cardiovascular and Autonomic Mediators: Baroreceptor Sensitivity and Heart Rate Variability
Baroreceptor sensitivity and heart rate variability are among the most important factors for evaluating the health and functionality of the cardiovascular and autonomic systems in those suffering from CP (Bruehl et al., 2018). BRS is a measure of the baroreflex, a homeostatic negative feedback loop important for maintaining healthy constant blood pressure levels in accordance with the requirements of a given situation (Mason et al., 2013). Changes in BRS may be involved in modulating the activity of endogenous pain modulatory systems (Kamibayashi and Maze, 2000). Recent research has also suggested that BRS may play a key role in the relationship between cardiovascular, respiratory activity, and pain dampening through the cardiovascular or central branches of the baroreceptor system (Jafari et al., 2017). HRV represents the change in the time interval between successive heartbeats and is used as an index of cardiac vagal tone (also known as cardiac vagal control), which is the contribution of the parasympathetic nervous system (i.e., vagal tone) to cardiac regulation (Brodal, 2004; Nahman-Averbuch et al., 2016; Laborde et al., 2017).
Among all of the time- and frequency-domain HRV parameters, the standard deviation of NN intervals (SDNN), the percentage of successive RR intervals that differ by more than 50 ms (pNN50), the high- frequency power (hf), and the root mean square of successive RR interval differences (RMSSD) are considered to reflect cardiac vagal tone (Telles et al., 2016; Laborde et al., 2017). However, due to their strong correlation (Kleiger et al., 2005) and ability to index self-regulation at the cognitive, emotional, social, and health levels (Thayer et al., 2009; McCraty and Shaffer, 2015), both RMSSD and hfHRV (specifically between 0.15 and 0.40 Hz) (Laborde et al., 2017) are considered the most optimal parameters for measuring cardiac vagal tone (Thayer and Lane, 2000).
The largest and broadest population study to date (Bruehl et al., 2018) has shown that beyond the effects of age, sex, and body mass index, those with CP have overall lower BRS and lower HRV in both the time domain (SDNN and rMSSD) and in the frequency domain (hfHRV) when compared to pain-free controls. In particular, those with CWP have a significantly lower BRS when compared to healthy subjects without CWP; persistent stress, pain behavior, and classical and operant conditioning mechanisms can all contribute in reducing BRS in those with CWP (Chung et al., 2008). Moreover, the inverse relationship between resting BP and pain sensitivity in healthy subjects becomes impaired in those with CWP (Meller et al., 2016). Instead of diminishing central sensitization and enhancing descending pain inhibition, elevated resting BP in those with CWP increases central sensitization and weakens descending pain inhibition. In turn, this can increase pain intensity (Coderre and Melzack, 1987; Chung and Bruehl, 2008).
A large study (Barakat et al., 2012) has also shown that there is a strong association between high pain intensity and low parasympathetic tone (as indicated by lower SDNN and lower RSA) for those with CWP when compared to healthy controls without CWP. The fact that low parasympathetic tone is not associated with the presence of CWP, but instead associated with high pain intensity, suggests that the experience of intense pain is a chronic stressor interfering with parasympathetic activity (Geenen and Bijlsma, 2010; Barakat et al., 2012; Evans et al., 2013; Pittig et al., 2013).
Pioneering research within the field of respiratory hypoalgesia has shown that DB performed with a high respiratory volume and low frequency could activate the anti-nociceptive effects of BRS (Dworkin et al., 1979; Dworkin et al., 1994) and concomitant increases in hfHRV (Triedman and Saul, 1994; Bruehl and Chung, 2004). This is in line with current evidence which does not support a direct causal association between DB and pain reduction, but instead, strongly suggests that a more indirect mediation through autonomic and cardiovascular changes is plausible (Jafari et al., 2017). We believe that an indirect mediation of pain through changes in HRV (autonomic) and BRS (cardiovascular) may be the most effective and plausible way DB can lower pain intensity and disability for those with CWP.
Physiological Mechanism: Diaphragmatic Resonance Frequency Breathing
Diaphragmatic Breathing (DB) is a pattern of expiration and inspiration in which most of the ventilatory work is executed by the diaphragm (Cahalin et al., 2002; Mosby, 2009). The diaphragm is a large, dome-shaped muscle located at the base of the lungs and is considered the most efficient muscle of breathing (Maitre et al., 1995; Cleveland Clinic, 2018a). DB is typically practiced by either laying in the supine position or sitting comfortably in a chair; the practitioner is instructed to emphasize a slow deep outward abdominal movement during inspiration and a slow deep inward abdominal movement during expiration (Cancelliero-Gaiad et al., 2014; Cleveland Clinic, 2018a). Factors which determine the physiological response of DB on pain are typically breadth frequency (breadths per minute) (Raghuraj et al., 1998; Park et al., 2013) and breadth volume (as indicated by respiratory depth) (Jafari et al., 2017).
The normal respiratory frequency for an adult at rest is around 12 to 20 breaths per minute whereas the respiratory frequency for performing DB can range from 5 to 8 breaths per minute (Shannahoff-Khalsa and Kennedy, 1993; Cleveland Clinic, 2018b). Many studies which have investigated DB for the treatment of CWP have been unclear in regard to what respiratory frequency patients should perform (Lehrer et al., 2000; Mohammed and Mohammed, 2014; Celhay et al., 2015; Jafari et al., 2017). Due to the significant relationship between low HRV and high pain intensity in CWP (Barakat et al., 2012), a DB frequency that can yield the greatest increase in hfHRV would be ideal. Experimental studies with healthy subjects (Pal and Velkumary, 2004; Jafari et al., 2017; Steffen et al., 2017) suggests that performing DB at a rate of around 6 breaths per minute (i.e., 0.10 Hz) may yield significant analgesic effects.
Breathing at a rate of 6 breaths per minute causes spontaneous oscillations in blood pressure (BP) to synchronize with BP oscillations caused by DB (Jafari et al., 2017). In turn, this can cause heart rate (HR) and breathing to synchronize, also known as RF breathing. The most common RF breathing rate is 5.5 or 6 breaths/min (Vaschillo et al., 2002) however, each person may have a unique RF breathing rate that typically ranges between 4.5 and 7.0 breaths/min. As people slow their breathing down and approach RF, the highest levels of HRV are typically obtained (Courtney et al., 2011; Steffen et al., 2017). Maximal fluctuations in HR (hfHRV) causes an increase in BP and BRS (Lehrer et al., 2003; Lagos et al., 2008).
Harmonic coupling between HRV, respiration, peripheral BP, and skin blood flow in a 0.15 Hz rhythm band (range: 0.12–0.18 Hz) has been demonstrated in healthy long- term practitioners of autogenic training (AT), a practice which uses visual imagery, body awareness, and DB exercises to promote a state of deep relaxation (Perlitz et al., 2004). In regard to pain treatment, medium-range positive effect sizes of AT and of AT versus control in a meta-analysis were found for several common symptoms and conditions inherent in those with CWP, some of which include somatoform pain disorders (unspecified type), anxiety disorders, and functional sleep disorders (Stetter and Kupper, 2002). Even though breathing at RF does matter when considering the optimal means of endogenously achieving hfHRV while increasing BRS (Vaschillo et al., 2002), it is still not clear whether breathing at RF would help treat CWP (Downey and Zun, 2009).
Efferent parasympathetic activity to the heart (i.e., cardiac vagal tone) elevates during expiration relative to inspiration due to the central respiratory gating of vagal outflow (Eckberg, 2003) and stimulation of the baroreceptors (Stancák et al., 1991b; Jafari et al., 2017). Prolonged duration of the exhalation phase during DB causes cardiac vagal tone to increase along with hfHRV across the entire respiratory cycle (Strauss-Blasche et al., 2000). FMS patients who breathe at half their normal rate are able to decrease pain and depressive symptoms more than when they are breathing normally (Zautra et al., 2010). This strongly suggests that the vagus nerve may be a prime target when considering a central mechanism responsible for producing respiratory hypoalgesia in CWP.
Central Mechanism: Vagal Nerve
The vagal nerve is the tenth cranial nerve composed of approximately 80% afferent fibers (which carry essential information from the body to the brain) and 20% efferent fibers (which send signals from the brain to the body) (Howland, 2014). Vagus nerve stimulation (VNS), which typically involves electrical stimulation of the vagal nerve, is an approved therapy for both refractory epilepsy and treatment-resistant depression (Howland, 2014; Vonck et al., 2014). Due to its central role in the bidirectional transmission and mediation of sensory information between the brain and the body (Howland, 2014), the vagus nerve may also be a promising mechanism for potentially treating the pathophysiology of CWP.
Experimental studies on animals (Ren et al., 1993, 1988) and preliminary intervention trials on humans (Lange et al., 2011; Busch et al., 2013) have shown that VNS can modulate multiple pathophysiological mechanisms inherent in CWP: VNS has shown to strongly reduce peripheral inflammatory cytokines in animals and in humans (Tateishi et al., 2007; Meregnani et al., 2011), decrease sympathetic tone by modulating descending serotonergic and noradrenergic neurons (Randich and Gebhart, 1992), decrease malondialdehyde (a biological marker of oxidative stress) (Pavithran et al., 2008), reverse pain-related brain activity patterns by reducing hippocampal and amygdala activity and increasing insular cortical and left prefrontal cortex activity (Kraus et al., 2007), and drive the antinociceptive effects of opioids and their derivatives (Tarapacki et al., 1992; De Couck et al., 2014).
VNS as a means of pain treatment has been traditionally administered through invasive procedures, known as invasive VNS (iVNS), which typically involve the surgical implantation of electrodes around the cervical vagus nerve (Chakravarthy et al., 2015). iVNS has a high risk for adverse events that include voice alteration, paresthesia, cough, headache, dyspnea, pharyngitis, and pain at the site of stimulation (Ben-Menachem et al., 2015). These adverse events often require a decrease in stimulation strength or even permanent deactivation and/or removal of the iVNS device. An effective non-invasive alternative to iVNS is transcutaneous VNS (tVNS). The tVNS system sends electrical impulses through the skin (transcutaneous) of the outer ear straight into the auricular branch of the vagus nerve (Peuker and Filler, 2002). Intensity, pulse duration, and frequency of the tVNS can be adjusted accordingly (Frangos et al., 2015).
Even though a number of studies using high intensity tVNS have not found any major side-effects, tVNS can still be accompanied by slight pain, burning, tingling, or itching sensations near the sight of the electrodes (Kraus et al., 2007; Dietrich et al., 2008). tVNS devices, like implantable VNS systems, are expensive to obtain, maintain, and have a narrow patient distribution (Howland, 2014). There is also no scientific consensus regarding the frequency and strength of tVNS stimulation for pain treatment (Chakravarthy et al., 2015) nor is there a clear understanding of how a constant pulse frequency mirrors endogenous vagal nerve activity (it likely does not communicate in consecutive 30 s intervals as most of the tVNS devices do) (Chapleau and Sabharwal, 2011).
Another important factor to consider is that the vagus nerve is not one uniform structure. It is instead composed of a diversity of molecularly distinct neuron types with different anatomical projections and functions (Chang et al., 2008). Artificial means to either transcutaneously or surgically stimulate the entire vagus nerve without cell specificity may be a main cause of unwanted side effects and lack of effect in CWP patients. Habituation (the loss of efficacy over time) or the appearance of new adverse events during chronic therapy limits VNS usefulness and should be assessed (Morris and Mueller, 1999). In addition, the risk, cost, and benefits of each type of vagal nerve–enhancing intervention, in relation to pain reduction and side effects, must be considered (De Couck et al., 2014). Therefore, DB as a means of endogenously stimulating the vagal nerve may be a better option for CWP patients.
Various forms of paced slow breathing have shown to influence brain electrical activity which may be mediated by VNS arising from the diaphragm (Stancák et al., 1991a, 1993). This cardio-respiratory stimulation of the vagus nerve may explain some of the overall positive emotional and cognitive benefits of DB (Howland, 2014). DB as a means of VNS may potentially decrease the pathophysiological processes involved in central sensitization as seen in CWP. This action may be the mechanism by which VNS reduces widespread musculoskeletal pain in FMS and other comparable pathologies (Lange et al., 2011; Chakravarthy et al., 2015). Among the many distinct neuron types within the vagus nerve are nerve fibers that specifically innervate the lungs and airways and which have been found to be vital for DB. These sensory neurons provide critical information needed to control respiration rate and regulate airway tone (Widdicombe, 2001; Canning et al., 2006). Within the airways, these vagal sensory neurons detect markers of inflammation, illness, and the mechanical stretch of the lungs during cycles of inhalation and exhalation while performing DB (Widdicombe, 2001; Carr and Undem, 2003).
Afferent vagal axons enter the brain bilaterally and primarily target the nucleus of the solitary tract (NTS), the first synapse in the baroreflex. This brainstem nucleus transmits sensory information to the limbic system and other deeper brain structures (Berthoud and Neuhuber, 2000; Kubin et al., 2006; Howland, 2014) and acts as an important interface between autonomic and regulatory centers within the brainstem and the central nervous nociceptive system (Bruehl and Chung, 2004; Duschek et al., 2013). This permits a central modulation of both cardiorespiratory and nociceptive activity (Chalaye et al., 2009; Jafari et al., 2017). The baroreceptor system connects the NTS with higher cerebral regions related to pain emotion, cognition, and autonomic control such as the periaqueductal gray, nucleus raphe magnus, locus coeruleus, anterior cingulate cortex, hypothalamus, and thalamus (Duschek et al., 2013). The periaqueductal gray’s involvement in central pain processing implies that local alterations within this region during DB may underlie a main component of the antinociceptive effects of VNS in humans (Kirchner et al., 2000; Henry, 2002; Subramanian and Holstege, 2010). The ability of VNS to reverse pain-related brain activity patterns during DB and target both affective and cognitive networks associated with pain raises the question as to whether a psychological mechanism could potentially amplify these reversal effects (Jafari et al., 2017).
Psychologically, pain can be perceived cognitively (as measured by the intensity of aching, burning, or stinging) (Turk and Rudy, 1992) and affectively (as measured by the unpleasantness of those sensations) (Frangos et al., 2017). Attentional modulation of pain preferentially affects perceived pain intensity, whereas the affective modulation of pain (dependent on one’s mood) preferentially modulates the unpleasantness of pain (Villemure et al., 2003; Loggia et al., 2008). This is highlighted by the fact that dissociable neural networks of attention and mood exist in regard to the modulation of pain intensity and unpleasantness (Legrain et al., 2009; Villemure and Bushnell, 2009). Even though pain intensity is frequently recommended as the primary indicator for determining intervention efficacy (Younger et al., 2009), it has been argued that pain intensity is not the best measure of the success of CP treatment (Ballantyne and Sullivan, 2015). Pain which is initially associated with the classic sensory “pain connectome” is later associated with brain regions involved in emotion and reward — over time, pain intensity becomes linked less with nociception and more with emotional and psychosocial factors (Hashmi et al., 2013; Ballantyne and Sullivan, 2015). The trending positive effects of VNS on various cognitive and affective processes are a further indication that psychological factors should be considered in studies and treatments investigating vagal pain modulation (Frangos et al., 2017).
Cognitive Psychological Mechanism: Non-Directive Meditation
Meditation encompasses a broad family of complex emotional and attentional regulatory training regimes that can be roughly categorized into three separate groups dependent upon the type of attention being practiced. Focused Attention (FA) meditation entails the voluntary focusing of attention on a chosen object or stimulus (usually the breath). Whenever attention wanders away from the breath, the meditator tries to quickly detect mind wandering and gently, but firmly, brings their attention back to the physical sensation of the breath (Brewer et al., 2011). Open Monitoring (OM) meditation involves a non-reactive monitoring of the content of inner and outer experiences from moment to moment (Lutz et al., 2008b). During OM meditation, the practitioner pays attention to whatever comes into and out of awareness — whether it may be a thought, emotion, or body sensation — without holding onto it or changing it in any way (Brewer et al., 2011). Non-directive meditation is somewhat of a combination of the two: where the presence of spontaneously occurring thoughts, images, sensations, memories, and emotions is accepted without actively directing attention toward them (FA) or away from them (OM) (Ellingsen and Holen, 2008; Nesvold et al., 2012). A practitioner of ND effortlessly places a relaxed focus of attention on a mental or audible sound (such as the non-semantic sound of an inhalation and exhalation) while non-judgmentally allowing the focus of their attention to shift toward spontaneously occurring thoughts, images, sensations, memories, or emotions (Davanger et al., 2010).
Chronic widespread pain patients who report high pain intensity display cognitive deficits and show significantly impaired performance on cognitively demanding tasks when compared to CWP patients with low pain intensity and healthy controls (Eccleston, 1995; Hart et al., 2000). The difficulty for CWP patients to sustain task-relevant attention causes pain-related anxiety, pain hypervigilance, pain catastrophizing, and long-term cognitive distress (Sullivan et al., 1995; Crombez et al., 2005). Attention diversion and attention allocation (James, 2013) (two skills trained during FA meditation) have been shown to reduce pain-related anxiety, pain hypervigilance, and pain interference and increase executive functioning for patients diagnosed with several CP conditions (Elomaa et al., 2009). Experimental studies comparing the efficacy of OM meditation practiced with DB (OM-DB) and FA meditation practiced with DB (FA-DB) at the same respiration rates (7 cycles per minute) and depths (2 cm amplitude/cycle) show that OM-DB significantly increases cold and hot pain threshold and attenuates pain perception significantly more than FA-DB in healthy adults (Busch et al., 2012) and is accompanied by concomitant changes in cardiac activity similar to what is observed during DB (Chalaye et al., 2009). However, as pain transitions from acute to chronic, there is an accompanying neurobiological shift toward emotionally related circuitry within the brain (Hashmi et al., 2013). The transition of pain from a sensory, cognitive, and nociceptive state to becoming more of an emotional burden is reflected neurologically within the default mode network (DMN) of those suffering from CWP. This is imperative to consider when choosing a suitable meditation that can not only treat cognitive functioning and pain, like FA and OM, but also modulate affective functioning in CWP.
fMRI analyses show that among the five major resting-state networks, only the DMN consistently exhibits altered spatial extent and functional connectivity properties in those suffering from CP when compared to healthy controls (Baliki et al., 2014). The DMN participates in episodic memory (Zysset et al., 2002), the monitoring and detection of internal salient events (Raichle et al., 2001), and affective processing (Xu et al., 2014). DMN functional connectivity in patients with several CP conditions shows that as pain becomes chronic, the DMN increases coupling between pain-related regions and affective regions such as the insular cortex — a brain region that signals both the sensory and affective properties of CP (Apkarian et al., 2011; Baliki et al., 2014). Conversely, a reduction of the intrinsic DMN connectivity to the insula in FMS patients following 4 weeks of acupuncture was shown to be strongly correlated to reductions in pain (Napadow et al., 2012).
It has been suggested that abnormal DMN coupling and communication with other affective brain systems in CWP may be driven by attention to pain in daily life (Letzen and Robinson, 2017). Those who suffer from CP report that their attention to ongoing pain often varies (Viane et al., 2004) and that the intensity of their pain can fluctuate on short time scales (seconds/minutes) (Foss et al., 2006). These daily fluctuations of attention and pain intensity involve constant interactions between the DMN and the antinociceptive system — an interaction which may determine the course of pain-related structural brain reorganization and CP prognosis (Kucyi et al., 2013). A meditation that has shown to modulate attention to pain in respect to emotion is ND meditation.
ND meditation, which permits mind wandering, involves a more extensive activation of brain areas associated with episodic memories and emotional processing, than during FA meditation, OM meditation, or regular rest (Xu et al., 2014). Most mindfulness practices view mind wandering as a distraction and a gateway to rumination, anxiety and depression (Sood and Jones, 2013; Xu et al., 2014). These practices make it their goal to reduce mind wandering and its potentially negative consequences (Brewer et al., 2011; Sood and Jones, 2013). However, mind wandering and activation of the DMN during ND meditation may serve introspective and adaptive functions beyond rumination and daydreaming (Ottaviani et al., 2013) — especially for those with CWP.
Stronger structural connectivity between the periaqueductal gray and the DMN is associated with the ability to mind wander away from pain and thus treat it as a non-distractor (Kucyi et al., 2013). By engaging in ND meditation, patients with CWP could possibly stimulate and rewire the DMN by allowing thoughts, images, sensations, memories, and emotions related to their pain to emerge and pass freely without actively controlling, escaping, or pursuing them (Xu et al., 2014) — over time this may reduce stress by increasing awareness and acceptance of pain as an emotionally charged experience (Ellingsen and Holen, 2008; Lutz et al., 2008a; Sood and Jones, 2013). ND meditation may teach a CWP patient to increase their ability to accept and tolerate the stressful and emotional burden of ongoing pain during the meditation and also outside of it (Davanger et al., 2010).
Functional connectivity between the DMN and brain regions associated with emotion regulation (i.e., the insula and parahippocampus) in patients diagnosed with major depressive disorder (commonly co-morbid in those with CWP) has also been shown to decrease after 1 month of tVNS compared to sham stimulation. The change in depression severity significantly correlated with functional connectivity changes between the DMN and regions that are implicated in both pain modulation and emotion, such as the anterior insula and anterior cingulate cortex (Fang et al., 2016; Su et al., 2016). However, investigations of vagal pain modulation do not reliably report the preferential modulation of affect on pain unpleasantness even though behavioral and brain imaging studies show that tVNS improves affect and produces functional changes in brain regions where pain modulation and affect converge (Frangos et al., 2017). Investigations which combine DB (as a means of vagal innervation) and ND meditation may be able to display some of the psychobehavioral changes that can occur in patients with CWP.
A study (Mehling et al., 2005) compared the effects of a 6–8 week breath therapy intervention (a type of ND meditation combined with DB) and high-quality, extended physical therapy on pain, disability, and emotional wellbeing as expressed in diary entries for patients diagnosed with chronic low back pain (cLBP). Researchers found that the pre to post-intervention changes in standard low back pain measures of pain and disability were comparable in both groups. However, major differences between groups appeared for emotional effects as displayed in patient diaries. cLBP patients randomized to the ND breath therapy intervention had diary entries with emotionally richer insights about their pain and coping with stress with few or no entries in the physical therapy group’s diaries. Interestingly, the more gentle and breath-focused the physical therapy was, the more similar the emotional diary statements were to breath therapy such as: “calmness,” “less anxiety,” “sense of emotional strength,” “encouraged,” “uplifting,” and “more emotional awareness” (Mehling et al., 2005).
The affective interoception seen in these diary statements as a result of an ND and DB- based therapy intervention reflect the neurobiological activity seen in brain regions, such as the insula, which result from VNS (Critchley et al., 2004; Frangos et al., 2015). The anatomy of interoceptive processing indicates a convergence of signals derived from the spine and the vagus nerve which travel toward cortical representations within the insular cortex (Craig and Craig, 2009). Interoception seems to be dependent upon a combination of both anatomy and motivational content (Craig and Craig, 2009); physiological sensations, such as pain, and organ signals are carried centrally by afferents that mostly ascend the spinal laminar 1 spinothalamic tract. This suggests a dedicated interoceptive-motivational pathway (Critchley and Garfinkel, 2017).
Affective Psychological Mechanism: Motivation
Preclinical and clinical evidence shows that tVNS simultaneously modulates both pain and mood, yet little is still known about possible indirect descending effects of altered mood states on pain perception for those suffering from CWP. Previous studies have shown that both positive and negative mood states can modulate the affective dimension of pain unpleasantness (Frangos et al., 2017). CWP patients are detrimentally affected by negative emotional states and attitudes that fluctuate on a daily basis which can exacerbate their pain symptoms (Haythornthwaite and Benrud-Larson, 2000; Schanberg et al., 2000; Frangos et al., 2017). Yet positive emotions, such as resiliency and optimism, can sustain CWP wellbeing and recovery (Ong et al., 2010; Sturgeon and Zautra, 2010) and may also be a promising means of treating the inflammatory etiology of CWP (Kox et al., 2014; van Middendorp et al., 2016). Due to the fact that systemic low-grade inflammation is associated with CWP (Gerdle et al., 2017), utilizing motivation and positive treatment expectancy may by an important treatment factor to consider. Therefore, identifying the interoceptive factors that influence pain coping and positive treatment expectancies could potentially help clinicians facilitate the use of adaptive coping strategies for treating CWP patients (Jensen et al., 1991).
Patients with CWP show significant anatomical and functional changes within reward/motivational circuitry within the brain that strengthen emotional and affective pain mechanisms (Apkarian et al., 2009; Apkarian et al., 2013). These maladaptive changes in aversive/motivational circuits are a challenge for CWP treatment (Navratilova and Porreca, 2014). However, targeting reward/motivation circuits can be a source for treatment that may provide a path for normalizing the neurobehavioral consequences of CWP and help surpass symptomatic management (Navratilova and Porreca, 2014).
Pain can be considered a homeostatic emotion (Craig and Craig, 2009) (such as hunger, thirst, or the desire to sleep) — a mechanism which involves receptors that detect internal imbalances (i.e., sensations) and aversive emotions that demand a behavioral response (i.e., motivation) to ensure the organism takes proper action to restore homeostasis (Denton et al., 2009). Therefore, pain can produce a strong motivational drive which promotes escape or, in the case of CWP, seek relief (Craig and Craig, 2009). Due to their fundamental role in survival, the basic neurological networks of reward, expectation, and motivation have evolved early and are conserved across species (Andreatta et al., 2012). The evolutionary role of negative (pain) and positive (relief) affective states is to elicit motivations that typically result in escape/avoidance and approach behaviors (Craig and Craig, 2009) — this allows an individual in pain to learn how to predict painful or relieving situations and/or triggers in the future (Wiech and Tracey, 2013). Even though ‘pain relief as reward’ has been a driver for human survival and wellbeing (Leknes et al., 2011), the constant daily demand for pain relief in those suffering from CWP can actually lead to the suppression of other emotions (i.e., natural rewards). This in turn can potentially lead to anhedonia (reward deficit state) and diminished quality of life (Simons et al., 2014).
Multilevel modeling analyses (Zautra et al., 2005) indicate that weekly elevations of pain and stress predict increases in negative affect in patients with CWP/FMS and that greater positive affect predicts lower levels of pain. Research investigating the relationships between CP patients’ dispositional optimism and pessimism and the coping strategies they use has found that there is a positive relationship between optimism and the use of active coping strategies (i.e., handling the pain or carry on functioning despite the pain) and pessimism and the use of passive coping strategies (i.e., giving control over pain to another person or allowing pain to adversely affect other areas of the patient’s life) (Ramírez-Maestre et al., 2012). Active coping is associated with low levels of pain, anxiety, depression and impairment and high levels of functioning whereas passive coping is related to high levels of pain, anxiety, depression and impairment and low levels of functioning for those suffering from a variety of CP conditions including CWP (Lin and Ward, 1996; Ramírez-Maestre et al., 2012). If left untreated, the neurologically affective quality of CWP has the potential to increase emotionally related pain catastrophizing which can predict the future onset of CP severity (Picavet et al., 2002; Sullivan et al., 2001a,b) and increase pro-inflammatory cytokines (Koch et al., 2007).
Emerging evidence suggests that systemic low-grade inflammation is associated with CWP and that the presence of inflammation could promote the spreading of pain, a hallmark sign of CWP (Gerdle et al., 2017). A multivariate, explorative, cross-sectional study (Gerdle et al., 2017) found that eleven pro-inflammatory proteins are significantly differentiated between healthy controls and CWP patients. Positive significant correlations exist between several proteins and pain intensity in CWP patients (Gerdle et al., 2017). However, positive optimism-inducing expectancies about health can induce immune responses that may directly and positively influence health and treatment outcomes for CWP. Motivation and expectation play major roles in the treatment outcomes for a wide variety of immune-mediated conditions and are shown to strengthen or mimic the effects of regular long-term therapies (van Middendorp et al., 2016).
The psychological and emotional state of an individual can have a significant impact on pain perception (Craig and Craig, 2009; Wiech and Tracey, 2009; Bushnell et al., 2013). Predictions about future (expected) pain or relief have shown to significantly influence the actual pain or analgesia that is experienced. Positive treatment expectancy produces heightened analgesia (placebo analgesia) (Atlas and Wager, 2012) while negative expectancy may exaggerate pain (nocebo) (Tracey, 2010; Doering and Rief, 2012). BOLD-fMRI measurements taken of the human spinal cord demonstrate that expectation of pain relief (placebo analgesia) directly reduces nociceptive processing in the dorsal horn of the spinal cord, presumably via intrinsic descending inhibitory mechanisms (Craig and Craig, 2009; Eippert et al., 2009). A proof-of-principal study (van Middendorp et al., 2016) also found that generalized outcome expectancy optimism is a potential determinant of the autonomic and immune response to an intravenously administered bacterial endotoxin (2 ng/kg Escherichia coli endotoxin) in healthy subjects after a short-term training program consisting of meditation, breathing exercises, and cold exposure.
A higher degree of optimism in subjects randomized to a training program consisting of meditation, breathing exercises, and cold exposure was associated with profoundly higher plasma epinephrine levels during the intravenous administration of the bacterial endotoxin followed by a more rapid and profound increase in anti-inflammatory IL-10 levels when compared to those in the non- trained group. A more positive expectation of the effects of the meditation, breathing, and cold exposure training on the psychophysiological reaction to the bacterial endotoxin was associated with lower flu-like clinical symptoms and lower subsequent pro- inflammatory TNF-α, IL-6, and IL-8 levels than the non- trained group (van Middendorp et al., 2016). The researchers noted that the DB breathing techniques practiced by the trained individuals mainly accounted for the increase in epinephrine and subsequent attenuation of the inflammatory response (Kox et al., 2014). Inflammatory conditions that produce or are induced by pain may also improve with DB vagal nerve innervation as descending vagal signals activate anti-inflammatory pathways that suppress secretion of pro-inflammatory cytokines during tVNS (e.g., TNFα and IL-1 IL β) (Borovikova et al., 2000), which could subsequently ameliorate associated pain (Yuan and Silberstein, 2016; Frangos et al., 2017).
The signaling of systemic inflammation is communicated to the brain via neural (predominantly vagus nerve) pathways, humorally via circulating cytokines, and directly via immune cells (Zaki et al., 2012). Chronic states of inflammation, as seen in CWP (Gerdle et al., 2017), influence emotion through a coordinated set of motivational changes conceptualized as ‘sickness behaviors’. These behaviors include fatigue, anhedonia, social withdrawal and irritability — all symptoms which are commonly shared with depression (de Heer et al., 2014; Harrison, 2016)and seen in CP patients (Harris, 2014). Subjective interoceptive experience which is generated by ND meditation and DB may help CWP patients generate new predictions and expectations about information (i.e., pain) coming from inside the body (Pacheco-López et al., 2006; Critchley and Garfinkel, 2017). Efferent (i.e., top-down) predictions concerning the state and outcome of the body (i.e., “I will feel calmer and less pain from this treatment”) is expressed in the autonomic nervous system, in endocrine, and in immune responses (Critchley and Garfinkel, 2017) which can beneficially effect a patient’s peripheral physiology (Seth, 2013; Seth and Friston, 2016). In turn, emotions and feelings arise through the interaction of descending bodily predictions (i.e., “I will feel calmer and less pain from this treatment”) through autonomic drive and ascending prediction errors (i.e., chronic stress and pain).
Evaluating pain-motivated behaviors can provide a path for the assessment of new treatment efficacy for CWP with a high likelihood of translational relevance. Due to the current notion that CWP may partly be an immune-mediated condition, this evidence raises the question as to whether motivation and expectation should be targeted and implemented within CWP treatment, especially in regards to a ND meditation and DB intervention.
Motivational Non-Directive Resonance Breathing: From Theory to Practice
In order to test whether MNRB is an effective psychophysiological intervention for endogenously treating pain intensity and disability in those who suffer from CWP, a randomized controlled clinical trial (Clinical Trials Identifier: NCT03180554) lead by the lead author (C.E.P.) and co-author (H.B.J.) in the Spring of 2019 will compare and investigate the treatment efficacy of MNRB and tVNS on patients diagnosed with CWP.
Consenting CWP patients (N = 112) who are referred to the Department of Pain Management and Research at Oslo University Hospital, Ullevål, in Oslo, Norway, will be randomized into one of four independent groups. Half of these participants (N = 56) will be randomized to either an experimental tVNS group or a sham tVNS group. The other half (N = 56) will be randomized to either an experimental MNRB group or a sham MNRB group. Both experimental and sham treatment interventions will be delivered twice per day at home, 15 min/morning and 15 min/evening, for a total duration of 2 weeks. Participants are invited to the clinic twice for pre- and post-intervention data collection. The primary outcomes are changes in photoplethysmography measured HRV and self-reported average pain intensity measured by the numeric rating scale. Secondary outcomes include changes in pain detection threshold, pain tolerance threshold, and pain pressure limit determined by computerized pressure cuff algometry as well as blood pressure and health related quality of life.
Participants randomized to the experimental or sham MNRB treatment will utilize an innovative smartphone-based program called MNRB and a CE-approved respiratory gating device called BarTekTM designed by the lead author (C.E.P.) and engineered by Dr. Marcin Czub at the University of Wrocław in Wrocław, Poland. The MNRB program and BarTekTM device work in-sync in order to deliver and guide CWP patients in both the sham and experimental versions of MNRB. The BarTekTM respiratory gating device is attached to an elastic strap which is placed around the patient’s abdomen, below the rib cage and an inch above the navel (behind which the thoracic diaphragm is located) (Bains and Lappin, 2018). Throughout the MNRB session, a strain gauge circuit accurately measures the tension produced during RF breathing. Respiration frequency and depth are calculated with a high resolution analog digital converter within the BarTekTM device and transmitted to the MNRB smartphone program via Bluetooth.
MNRB is to be practiced at home, twice a day for 2 weeks, in a relaxed semi-Fowler position (30 degree tilt from the horizontal) with feet flat on the floor, hands on thighs, and palms facing upward. Ideally, MNRB should be practiced with a head tilt no more than 30 degrees from the horizontal (Mukai and Hayano, 1995) due to the fact during high-level tilt (30–90 degrees), the R-R interval and hfHRV progressively decrease with tilt angle (P < 0.001 for both) (Berna et al., 2014; Quintana et al., 2016). This relaxed sitting position is also conducive for patients who will be taking a 1-min HRV recording (Laborde et al., 2017) immediately before and after each MNRB session.
When in position, CWP patients strap the BarTekTM respiratory gating device around their abdomen, open the MNRB program on the smartphone, and are guided (Kniffin et al., 2014) from an average respiration rate of 12 breadths/min to a RF of 6 breadths/min. The average respiratory rate for a healthy adult at rest is typically defined as 12–20 breadths/min (Cleveland Clinic, 2018b) whereas patients diagnosed with FMS have shown to have a respiration rate of around 13.68 breadths/min (Zautra et al., 2010). Participants are instructed to use the diaphragm to breathe in slowly through the nose to full inspiratory capacity and exhale to full expiratory capacity through pursed lips by tightening and pulling the stomach back toward the spine. Participants are instructed to retain a 1:2 inhale: exhale ratio in order to efficiently increase hfHRV across the entire respiratory cycle (Strauss-Blasche et al., 2000) and retain their breadth after full inhalation and full exhalation. Inclusion of a post-exhalation rest period significantly decreases HR (p < 0.001) and increases hfHRV (p < 0.05) (Russell et al., 2017). Participants are further instructed not to move or to speak and to allow the chest to remain immobile throughout the entirety of the session (Mosby, 2009; Cleveland Clinic, 2018a).
The MNRB session begins with a transition period during which patients are taken from an average respiration frequency of 12 breadths/min to a RF of 6 breadths/min. During this transition period, patients are to attend to a respiration guide while listening to a 110 Hz frequency which has been shown to increase hfHRV (Hori et al., 2005). While breathing with the respiration guide, participants are also provided with a series of written sentences that appear and disappear on the smartphone screen. These sentences are of an affective and motivational tone which encourage patients to reason about emotional issues that may surround and define their pain.
Emotional information derived from their MNRB practice can help CWP patients to become motivated to solve problems and achieve goals on a daily basis. In turn, this may be helpful for increasing emotional intelligence (Mayer J.D. et al., 2008). Emotional intelligence is highly predictive of important aspects of social/interpersonal functioning and professional success (Brackett et al., 2006; Moslehi et al., 2015). This can potentially benefit CWP patients in particular who suffer from high rates of long-term sick leave (Mose et al., 2016) and lack interpersonal skills (Hayaki et al., 2016). The adaptive use of emotional intelligence to become motivated and achieve goals in regards to increasing ones sense of emotional resilience and interoception requires the integration of many capacities that include: self-awareness, subjective perceptions, reasoning, and skilled behavioral responses (Killgore et al., 2017).
When CWP patients arrive at their target RF of 6 breadths/min following the transition period, the MNRB screen begins to darken and the respiratory guide disappears while the inhale/exhale sound guide along with the 110 Hz background frequency remains. At this moment, patients are invited to close their eyes and engage in a ND state of mind. Cardiac parasympathetic nervous activity indicated by hfHRV has been found to increase more while listening to a 110 Hz sine wave when the eyes are closed as compared to when they are open (Hori et al., 2005). As described previously, patients are to engage in a flexible and nonjudgmental cognitive state between the sensation of breathing and any spontaneous stimuli which may arise moment by moment; attention is permitted to shift toward and away from spontaneously occurring thoughts, feelings, and sensations related or unrelated to their pain, and back to the repetition of the inspiration/expiration sound. This is unlike standardized mindfulness practices where sustained attention is required to maintain focus on the breath while cognitive control is required to detect mind wandering (Moore et al., 2012).
If the patient continues to correctly breathe at the RF of 6 breadths/min the respiration inhale/exhale sound guides silence and the patient is only left with listening to the 110 Hz auditory background tone. Continuing to breathe at RF will also cause this background tone to dissipate after a few breaths leaving the patient in complete silence. This teaches and entrusts the patient to embody the treatment on their own terms which in turn may lead to a sense of mastery over a 2 week period. Considering the high costs for running contemplative research trials, the type of meditation practice under investigation, and the multiple outcomes being explored, it is important to reevaluate the typical 4–8 week intervention duration of typical mindfulness-based meditation practices for treating specific psychophysiological parameters in CWP patients.
Most researchers hold the assumption that meditation practice has its effects in a cumulative way through long-term practice. However, current research (Zeng et al., 2017) shows that short-term influences of meditation practice have a more promising effect upon clinical outcomes and that continual meditation practice may not be necessary for maintaining effects (Cohn and Fredrickson, 2010). Therefore, this study will employ a 2-week meditation intervention where both short-term (i.e., daily) and long-term changes (i.e., changes in pre- to post-intervention measures) of self-reported pain and HRV effect patterns will be analyzed in accordance with the three R procedure: resting (i.e., pre-intervention), reactivity (i.e., tVNS/MNRB treatment), and recovery (i.e., post-intervention) (Stein and Pu, 2012). Following this procedure will aide in determining the differential treatment effects of experimental versus sham MNRB.
Trials have attempted but failed to design sham breathing procedures for control groups simply due to the fact that the influence of the diaphragm muscle cannot be ruled out (Kapitza et al., 2010; Eherer et al., 2012). However, the BarTekTM device will allow us to see whether or not a participant randomized to the sham MNRB group has been utilizing their diaphragm during each treatment session. Participants in the sham MNRB group will practice MNRB with the same posture and time protocol as the experimental group (Chan et al., 2007; Russell et al., 2014). However, participants are instead instructed to breathe at the normal respiration rate for an adult (12 breadths/min) (Barrett and Ganong, 2013) by attentively following the visual respiratory pacer (Elstad, 2012) on the MNRB program while counting their breadth (Juel et al., 2017). There is no background frequency of 110 Hz playing during the sham MNRB session and only one sentence that remains on the screen for the entirety of the session which instructs participant to relax while breathing with the visual respiratory pacer indicated by the moving orb. Sham MNRB does not promote endogenous mastery of the treatment and remains on the screen for each treatment session.
Conclusion
Contemplative research is challenged to evaluate, measure, and explain the effects of meditation and other contemplative practices on health and well-being when compared to mainstream treatment regimens. Even though these practices are of great interest to the scientific and medical communities within the field of CWP research and management, objective measures to best assess their beneficial outcomes are lacking (Desbordes et al., 2014). Current findings on the effects of meditation practice are few and inconsistent for various chronic pain conditions — studies suffer from inconsistencies within intervention deliverability and type while other’s show relatively few associations between outcome variables and the amount of meditation practice (Zeng et al., 2017). Previous theories which include the neurovisceral integration model, the polyvagal theory, the biological behavioral model, the RF model, and the psychophysiological coherence model provide important insights in regards to how vagal tone is important to consider when optimizing psychophysiological health. However, these theories lack a formalized and integrated means of methodologically applying the theory to practice within the field of CWP treatment.
Clinical and self-report pain intensity is often used as the sole primary outcome for determining intervention efficacy in clinical trials employing mainstream and alternative treatment interventions for those suffering from CWP (Williams et al., 2012). Yet it has been argued that pain intensity may not the best indicator of effective CWP treatment (Ballantyne and Sullivan, 2015). Based upon this conjecture and research showing a strong association between high pain intensity and low HRV readings in CWP patients (Barakat et al., 2012) we have chosen HRV as our primary outcome of interest along with self- report pain intensity. This will provide us with a more robust evaluation of our medical hypothesis and reveal the autonomic, respiratory, circulatory, endocrine and mechanical influences of MNRB on pain over both a short and long-term time frame.
The current lack of mainstream and alternative treatment efficacy, safety, and reliability calls for the development of new treatment modalities, such as MNRB, that meet the biopsychosocial needs of those suffering from CWP. Motivational ND resonance breathing (MNRB) could be an innovative, effective, and noninvasive means of CWP treatment. To our knowledge, we are the first to propose such an intervention that could potentially target CWP etiological factors we believe to be imperative for successful treatment.
Author Contributions
CP is the lead and corresponding author for this work, responsible for the original conception and design of the chronic widespread pain treatment program presented and motivational ND diaphragmatic breathing. HJ interpreted and analyzed the biopsychosocial framework and psychological theory of the program in respect to chronic widespread pain treatment. CP and HJ revised the work critically for important intellectual content, approved the final version to be published, and are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding
This work was supported by the Department for Research and Innovation South-East Regional Health Authority, Norway (Project No. 2017046).
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
Andreatta, M., Fendt, M., Mühlberger, A., Wieser, M. J., Imobersteg, S., Yarali, A., et al. (2012). Onset and offset of aversive events establish distinct memories requiring fear and reward networks. Learn. Mem. 19, 518–526. doi: 10.1101/lm.026864.112
Andrews, P., Steultjens, M., and Riskowski, J. (2017). Chronic widespread pain prevalence in the general population: a systematic review. Eur. J. Pain 22, 5–18. doi: 10.1002/ejp.1090
Apkarian, A. V., Baliki, M. N., and Farmer, M. A. (2013). Predicting transition to chronic pain. Curr. Opin. Neurol. 26, 360–370. doi: 10.1097/WCO.0b013e32836336ad
Apkarian, A. V., Baliki, M. N., and Geha, P. Y. (2009). Towards a theory of chronic pain. Prog. Neurobiol. 87, 81–97. doi: 10.1016/j.pneurobio.2008.09.018
Apkarian, A. V., Hashmi, J. A., and Baliki, M. N. (2011). Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152(3 Suppl.), S49.
Atlas, L. Y., and Wager, T. D. (2012). How expectations shape pain. Neurosci. Lett. 520, 140–148. doi: 10.1016/j.neulet.2012.03.039
Bains, K. N., and Lappin, S. L. (2018). Anatomy, Thorax, Diaphragm. Treasure Island, FL: StatPearls Publishing.
Baliki, M. N., Mansour, A. R., Baria, A. T., and Apkarian, A. V. (2014). Functional reorganization of the default mode network across chronic pain conditions. PLoS One 9:e106133. doi: 10.1371/journal.pone.0106133
Ballantyne, J. C., and Sullivan, M. D. (2015). Intensity of chronic pain—the wrong metric? New Engl. J. Med. 373, 2098–2099. doi: 10.1056/nejmp1507136
Barakat, A., Vogelzangs, N., Licht, C. M., Geenen, R., MacFarlane, G. J., de Geus, E. J., et al. (2012). Dysregulation of the autonomic nervous system and its association with the presence and intensity of chronic widespread pain. Arthritis Care Res. 64, 1209–1216. doi: 10.1002/acr.21669
Barnes, P. M., Bloom, B., and Nahin, R. L. (2008). Complementary and Alternative Medicine Use Among Adults and Children: United States, 2007. National Health Statistics Reports No. 12. Hyattsville, MD: National Center for Health Statistics.
Barrett, K., and Ganong, W. (2013). Ganong’s Review of Medical Physiology. New York, NY: McGraw-Hill.
Bee, P., McBeth, J., MacFarlane, G. J., and Lovell, K. (2016). Managing chronic widespread pain in primary care: a qualitative study of patient perspectives and implications for treatment delivery. BMC Musculoskelet. Disord. 17:354. doi: 10.1186/s12891-016-1194-5
Ben-Menachem, E., Revesz, D., Simon, B. J., and Silberstein, S. (2015). Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Eur. J. Neurol. 22, 1260–1268. doi: 10.1111/ene.12629
Berna, G., Ott, L., and Nandrino, J. L. (2014). Effects of emotion regulation difficulties on the tonic and phasic cardiac autonomic response. PLoS One 9:e102971. doi: 10.1371/journal.pone.0102971
Berthoud, H. R., and Neuhuber, W. L. (2000). Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 85, 1–7.
Borgbjerg, F. M., Nielsen, K., and Franks, J. (1996). Experimental pain stimulates respiration and attenuates morphine-induced respiratory depression: a controlled study in human volunteers. Pain 64, 123–128. doi: 10.1016/0304-3959(95)00088-7
Borovikova, L. V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G. I., Watkins, L. R., et al. (2000). Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462. doi: 10.1038/35013070
Boudreau, D., Von Korff, M., Rutter, C. M., Saunders, K., Ray, G. T., Sullivan, M. D., et al. (2009). Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol. Drug Saf. 18, 1166–1175. doi: 10.1002/pds.1833
Brackett, M. A., Rivers, S. E., Shiffman, S., Lerner, N., and Salovey, P. (2006). Relating emotional abilities to social functioning: a comparison of self-report and performance measures of emotional intelligence. J. Pers. Soc. Psychol. 91, 780–795. doi: 10.1037/0022-3514.91.4.780
Breivik, H., Collett, B., Ventafridda, V., Cohen, R., and Gallacher, D. (2006). Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur. J. Pain 10, 287–333.
Brewer, J. A., Worhunsky, P. D., Gray, J. R., Tang, Y. Y., Weber, J., and Kober, H. (2011). Meditation experience is associated with differences in default mode network activity and connectivity. Proc. Natl. Acad. Sci. U.S.A. 108, 20254–20259. doi: 10.1073/pnas.1112029108
Brodal, P. (2004). The Central Nervous System: Structure and Function. Oxford: Oxford University Press.
Bruehl, S., and Chung, O. Y. (2004). Interactions between the cardiovascular and pain regulatory systems: an updated review of mechanisms and possible alterations in chronic pain. Neurosci. Biobehav. Rev. 28, 395–414. doi: 10.1016/j.neubiorev.2004.06.004
Bruehl, S., Olsen, R. B., Tronstad, C., Sevre, K., Burns, J. W., Schirmer, H., et al. (2018). Chronic pain-related changes in cardiovascular regulation and impact on comorbid hypertension in a general population: the tromsø study. Pain 159, 119–127. doi: 10.1097/j.pain.0000000000001070
Busch, V., Magerl, W., Kern, U., Haas, J., Hajak, G., and Eichhammer, P. (2012). The effect of deep and slow breathing on pain perception, autonomic activity, and mood processing—an experimental study. Pain Med. 13, 215–228. doi: 10.1111/j.1526-4637.2011.01243.x
Busch, V., Zeman, F., Heckel, A., Menne, F., Ellrich, J., and Eichhammer, P. (2013). The effect of transcutaneous vagus nerve stimulation on pain perception–an experimental study. Brain Stimul. 6, 202–209. doi: 10.1016/j.brs.2012.04.006
Bushnell, M. C., Čeko, M., and Low, L. A. (2013). Cognitive and emotional control of pain and its disruption in chronic pain. Nat. Rev. Neurosci. 14, 502–511. doi: 10.1038/nrn3516
Butler, S., Landmark, T., Glette, M., Borchgrevink, P., and Woodhouse, A. (2016). Chronic widespread pain—the need for a standard definition. Pain 157, 541–543. doi: 10.1097/j.pain.0000000000000417
Cahalin, L. P., Braga, M., Matsuo, Y., and Hernandez, E. D. (2002). Efficacy of diaphragmatic breathing in persons with chronic obstructive pulmonary disease: a review of the literature. J. Cardiopul. Rehabil. Prev. 22, 7–21. doi: 10.1097/00008483-200201000-00002
Cancelliero-Gaiad, K. M., Ike, D., Pantoni, C. B., Borghi-Silva, A., and Costa, D. (2014). Respiratory pattern of diaphragmatic breathing and pilates breathing in COPD subjects. Braz. J. Phys. Ther. 18, 291–299. doi: 10.1590/bjpt-rbf.2014.0042
Canning, B. J., Mori, N., and Mazzone, S. B. (2006). Vagal afferent nerves regulating the cough reflex. Respir. Physiol. Neurobiol. 152, 223–242. doi: 10.1016/j.resp.2006.03.001
Carr, M. J., and Undem, B. J. (2003). Bronchopulmonary afferent nerves. Respirology 8, 291–301. doi: 10.1046/j.1440-1843.2003.00473.x
Celhay, I., Cordova, R., Miralles, R., Meza, F., Erices, P., Barrientos, C., et al. (2015). Effect of upper costal and costo-diaphragmatic breathing types on electromyographic activity of respiratory muscles. Cranio 133, 100–106. doi: 10.1179/2151090314y.0000000011
Chakravarthy, K., Chaudhry, H., Williams, K., and Christo, P. J. (2015). Review of the uses of vagal nerve stimulation in chronic pain management. Curr. Pain Headache Rep. 19:54. doi: 10.1007/s11916-015-0528-6
Chalaye, P., Goffaux, P., Lafrenaye, S., and Marchand, S. (2009). Respiratory effects on experimental heat pain, and cardiac activity. Pain Med. 10, 1334–1340. doi: 10.1111/j.1526-4637.2009.00681.x
Chan, H.-L., Lin, M.-A., Chao, P.-K., and Lin, C.-H. (2007). Correlates of the shift in heart rate variability with postures and walking by time–frequency analysis. Comput. Methods Programs Biomed. 86, 124–130. doi: 10.1016/j.cmpb.2007.02.003
Chang, R. B., Strochlic, D. E., Williams, E. K., Umans, B. D., and Liberles, S. D. (2008). Vagal sensory neuron subtypes that differentially control breathing. Cell 161, 622–633. doi: 10.1016/j.cell.2015.03.022
Chapleau, M. W., and Sabharwal, R. (2011). Methods of assessing vagus nerve activity and reflexes. Heart Fail. Rev. 16, 109–127. doi: 10.1007/s10741-010-9174-6
Chiesa, A., and Malinowski, P. (2011). Mindfulness-based approaches: are they all the same? J. Clin. Psychol. 67, 404–424. doi: 10.1002/jclp.20776
Chiesa, A., and Serretti, A. (2011). Mindfulness-based interventions for chronic pain: a systematic review of the evidence. J. Altern. Complement. Med. 17, 83–93. doi: 10.1089/acm.2009.0546
Chou, R., Turner, J. A., Devine, E. B., Hansen, R. N., Sullivan, S. D., Blazina, I., et al. (2015). The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a national institutes of health pathways to prevention workshopeffectiveness and risks of long-term opioid therapy for chronic pain. Ann. Intern. Med. 162, 276–286. doi: 10.7326/M14-2559
Chung, O. Y., and Bruehl, S. (2008). The impact of blood pressure and baroreflex sensitivity on wind-up. Anesth. Analg. 107, 1018–1025. doi: 10.1213/ane.0b013e31817f8dfe
Chung, O. Y., Bruehl, S., Diedrich, L., Diedrich, A., Chont, M., and Robertson, D. (2008). Baroreflex sensitivity associated hypoalgesia in healthy states is altered by chronic pain. Pain 138, 87–97. doi: 10.1016/j.pain.2007.11.011
Coderre, T. J., and Melzack, R. (1987). Cutaneous hyperalgesia: contributions of the peripheral and central nervous systems to the increase in pain sensitivity after injury. Brain Res. 404, 95–106. doi: 10.1016/0006-8993(87)91359-x
Cohn, M., and Fredrickson, B. (2010). In search of durable positive psychology interventions: predictors and consequences of long-term positive behavior change. J. Posit. Psychol. 5, 355–366. doi: 10.1080/17439760.2010.508883
Coronado-Montoya, S., Levis, A., Kwakkenbos, L., Steele, R., Turner, E., and Thombs, B. (2016). Reporting of positive results in randomized controlled trials of mindfulness-based mental health interventions. PLoS One 11:e0153220. doi: 10.1371/journal.pone.0153220
Courtney, R., Cohen, M., and van Dixhoorn, J. (2011). Relationship between dysfunctional breathing patterns and ability to achieve target heart rate variability with features of “coherence” during biofeedback. Altern. Ther. Health Med. 17:38.
Craig, A. D., and Craig, A. D. (2009). How do you feel–now? The anterior insula and human awareness. Nat. Rev. Neurosci. 10, 59–70. doi: 10.1038/nrn2555
Critchley, H. D., and Garfinkel, S. N. (2017). Interoception and emotion. Curr. Opin. Psychol. 17, 7–14. doi: 10.1016/j.copsyc.2017.04.020
Critchley, H. D., Wiens, S., Rotshtein, P., Öhman, A., and Dolan, R. J. (2004). Neural systems supporting interoceptive awareness. Nat. Neurosci. 7:189. doi: 10.1038/nn1176
Crombez, G., Van Damme, S., and Eccleston, C. (2005). Hypervigilance to pain: an experimental and clinical analysis. Pain 116, 4–7. doi: 10.1016/j.pain.2005.03.035
Davanger, S., Ellingsen, Ø, Holen, A., and Hugdahl, K. (2010). Meditation-specific prefrontal cortical activation during acem meditation: an fMRI study. Percept. Mot. Skills 111, 291–306. doi: 10.2466/02.04.22.pms.111.4.291-306
De Couck, M., Nijs, J., and Gidron, Y. (2014). You may need a nerve to treat pain: the neurobiological rationale for vagal nerve activation in pain management. Clin. J. Pain 30, 1099–1105. doi: 10.1097/AJP.0000000000000071
de Heer, E. W., Gerrits, M. M., Beekman, A. T., Dekker, J., van Marwijk, H. W., de Waal, M. W., et al. (2014). The association of depression and anxiety with pain: a study from NESDA. PLoS One 9:e106907. doi: 10.1371/journal.pone.0106907
Denton, D. A., McKinley, M. J., Farrell, M., and Egan, G. F. (2009). The role of primordial emotions in the evolutionary origin of consciousness. Conscious. Cogn. 18, 500–514. doi: 10.1016/j.concog.2008.06.009
Desbordes, G., Gard, T., Hoge, E., Hölzel, B., Kerr, C., Lazar, S., et al. (2014). Moving beyond mindfulness: defining equanimity as an outcome measure in meditation and contemplative research. Mindfulness 6, 356–372. doi: 10.1007/s12671-013-0269-8
Dietrich, S., Smith, J., Scherzinger, C., Hofmann-Preiß, K., Freitag, T., Eisenkolb, A., et al. (2008). A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional mri/funktionelle magnetresonanztomographie zeigt aktivierungen des hirnstamms und weiterer zerebraler strukturen unter transkutaner vagusnervstimulation. Biomed. Tech. 53, 104–111. doi: 10.1515/bmt.2008.022
Doering, B. K., and Rief, W. (2012). Utilizing placebo mechanisms for dose reduction in pharmacotherapy. Trends Pharmacol. Sci. 33, 165–172. doi: 10.1016/j.tips.2011.12.001
Downey, L. V. A., and Zun, L. S. (2009). The effects of deep breathing training on pain management in the emergency department. South Med. J. 102, 688–692. doi: 10.1097/SMJ.0b013e3181a93fc5
Duschek, S., Werner, N. S., and Reyes del Paso, G. A. (2013). The behavioral impact of baroreflex function: a review. Psychophysiology 50, 1183–1193. doi: 10.1111/psyp.12136
Dworkin, B. R., Elbert, T., Rau, H., Birbaumer, N., Pauli, P., Droste, C., et al. (1994). Central effects of baroreceptor activation in humans: attenuation of skeletal reflexes and pain perception. Proc. Natl. Acad. Sci. U.S.A. 91, 6329–6333. doi: 10.1073/pnas.91.14.6329
Dworkin, B. R., Filewich, R. J., Miller, N. E., Craigmyle, N., and Pickering, T. G. (1979). Baroreceptor activation reduces reactivity to noxious stimulation: implications for hypertension. Science 205, 1299–1301. doi: 10.1126/science.472749
Eccleston, C. (1995). Chronic pain and distraction: an experimental investigation into the role of sustained and shifting attention in the processing of chronic persistent pain. Behav. Res. Ther. 33, 391–405. doi: 10.1016/0005-7967(94)00057-q
Eckberg, D. L. (2003). The human respiratory gate. J. Physiol. 548(Pt 2), 339. doi: 10.1113/jphysiol.2003.037192
Eherer, A. J., Netolitzky, F., Högenauer, C., Puschnig, G., Hinterleitner, T. A., Scheidl, S., et al. (2012). Positive effect of abdominal breathing exercise on gastroesophageal reflux disease: a randomized, controlled study. Am. J. Gastroenterol. 107, 372–378. doi: 10.1038/ajg.2011.420
Eippert, F., Finsterbusch, J., Bingel, U., and Büchel, C. (2009). Direct evidence for spinal cord involvement in placebo analgesia. Science 326:404. doi: 10.1126/science.1180142
Ellingsen, O., and Holen, A. (2008). “Meditation: a scientific perspective,” in Fighting Stress, eds S. Davanger and H. Hersoung (Oslo: ACEM), 11–35.
Elomaa, M. M., Williams, A. C., and Kalso, E. A. (2009). Attention management as a treatment for chronic pain. Eur. J. Pain 13, 1062–1067. doi: 10.1016/j.ejpain.2008.12.002
Elstad, M. (2012). Respiratory variations in pulmonary and systemic blood flow in healthy humans. Acta Physiol. 205, 341–348. doi: 10.1111/j.1748-1716.2012.02419.x
Evans, S., Seidman, L. C., Tsao, J. C., Lung, K. C., Zeltzer, L. K., and Naliboff, B. D. (2013). Heart rate variability as a biomarker for autonomic nervous system response differences between children with chronic pain and healthy control children. J. Pain Res. 6, 449–557. doi: 10.2147/JPR.S43849
Fang, J., Rong, P., Hong, Y., Fan, Y., Liu, J., Wang, H., et al. (2016). Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder. Biol. Psychiatry 79, 266–273. doi: 10.1016/j.biopsych.2015.03.025
Farias, M., Wikholm, C., and Delmonte, R. (2016). What is mindfulness-based therapy good for? Lancet Psychiatry 3, 1012–1013. doi: 10.1016/s2215-0366(16)30211-5
Foss, J. M., Apkarian, A. V., and Chialvo, D. R. (2006). Dynamics of pain: fractal dimension of temporal variability of spontaneous pain differentiates between pain states. J. Neurophysiol. 95, 730–736. doi: 10.1152/jn.00768.2005
Frangos, E., Ellrich, J., and Komisaruk, B. R. (2015). Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul. 8, 624–636. doi: 10.1016/j.brs.2014.11.018
Frangos, E., Richards, E. A., and Bushnell, M. C. (2017). Do the psychological effects of vagus nerve stimulation partially mediate vagal pain modulation? Neurobiol. Pain 1, 37–45. doi: 10.1016/j.ynpai.2017.03.002
Geenen, R., and Bijlsma, J. W. (2010). Deviations in the endocrine system and brain of patients with fibromyalgia: cause or consequence of pain and associated features? Ann. N. Y. Acad. Sci. 1193, 98–110. doi: 10.1111/j.1749-6632.2009.05290.x
Gerdle, B., Björk, J., Cöster, L., Henriksson, K. G., Henriksson, C., and Bengtsson, A. (2008). Prevalence of widespread pain and associations with work status: a population study. BMC Musculoskelet. Disord. 9:102. doi: 10.1186/1471-2474-9-102
Gerdle, B., Ghafouri, B., Ghafouri, N., Bäckryd, E., and Gordh, T. (2017). Signs of ongoing inflammation in female patients with chronic widespread pain: a multivariate, explorative, cross-sectional study of blood samples. Medicine 96:e6130. doi: 10.1097/MD.0000000000006130
Grossman, P., and Taylor, E. W. (2007). Toward understanding respiratory sinus arrhythmia: relations to cardiac vagal tone, evolution and biobehavioral functions. Biol. Psychol. 74, 263–285. doi: 10.1016/j.biopsycho.2005.11.014
Harrison, N. A. (2016). Brain Structures Implicated in Inflammation-Associated Depression. InInflammation-Associated Depression: Evidence, Mechanisms and Implications. Berlin: Springer, 221–248.
Hart, R. P., Martelli, M. F., and Zasler, N. D. (2000). Chronic pain and neuropsychological functioning. Neuropsychol. Rev. 10, 131–149.
Hashmi, J. A., Baliki, M. N., Huang, L., Baria, A. T., Torbey, S., Hermann, K. M., et al. (2013). Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain 136, 2751–2768. doi: 10.1093/brain/awt211
Häuser, W., Perrot, S., Sommer, C., Shir, Y., and Fitzcharles, M. A. (2017). Diagnostic confounders of chronic widespread pain: not always fibromyalgia. Pain Rep. 2:e598. doi: 10.1097/PR9.0000000000000598
Hayaki, C., Anno, K., Shibata, M., Iwaki, R., Kawata, H., Sudo, N., et al. (2016). Family dysfunction: a comparison of chronic widespread pain and chronic localized pain. Medicine 95:e5495. doi: 10.1097/md.0000000000005495
Haythornthwaite, J. A., and Benrud-Larson, L. M. (2000). Psychological aspects of neuropathic pain. Clin. J. Pain 16(2 Suppl.), S101–S105.
Henningsen, P., Zipfel, S., and Herzog, W. (2007). Management of functional somatic syndromes. Lancet 369, 946–955.
Henry, T. R. (2002). Therapeutic mechanisms of vagus nerve stimulation. Neurology 59(6 Suppl. 4), S3–S14.
Hilton, L., Hempel, S., Ewing, B. A., Apaydin, E., Xenakis, L., Newberry, S., et al. (2016). Mindfulness meditation for chronic pain: systematic review and meta-analysis. Ann. Behav. Med. 51, 199–213. doi: 10.1007/s12160-016-9844-2
Hofmann, S. G., and Asmundson, G. J. (2008). Acceptance and mindfulness-based therapy: new wave or old hat? Clin. Psychol. Rev. 28, 1–6. doi: 10.1016/j.cpr.2007.09.003
Hori, K., Yamakawa, M., Tanaka, N., Murakami, H., Kaya, M., and Hori, S. (2005). Influence of sound and light on heart rate variability. J. Hum. Ergol. 34, 25–34.
Ivanova, J. I., Birnbaum, H. G., Yushkina, Y., Sorg, R. A., Reed, J., and Sanjay Merchant, M. B. (2013). The prevalence and economic impact of prescription opioid-related side effects among patients with chronic noncancer pain. J. Opioid Manag. 9, 239–254. doi: 10.5055/jom.2013.0165
Jafari, H., Courtois, I., Van den Bergh, O., Vlaeyen, J. W., and Van Diest, I. (2017). Pain and respiration: a systematic review. Pain 158, 995–1006. doi: 10.1097/j.pain.0000000000000865
Järemo, P., Arman, M., Gerdle, B., Larsson, B., and Gottberg, K. (2017). Illness beliefs among patients with chronic widespread pain-associations with self-reported health status, anxiety and depressive symptoms and impact of pain. BMC Psychol. 5:24. doi: 10.1186/s40359-017-0192-1
Jensen, M. P., Turner, J. A., and Romano, J. M. (1991). Self-efficacy and outcome expectancies: relationship to chronic pain coping strategies and adjustment. Pain 44, 263–269. doi: 10.1016/0304-3959(91)90095-f
Juel, J., Brock, C., Olesen, S. S., Madzak, A., Farmer, A. D., Aziz, Q., et al. (2017). Acute physiological and electrical accentuation of vagal tone has no effect on pain or gastrointestinal motility in chronic pancreatitis. J. Pain Res. 10, 1347–1355. doi: 10.2147/JPR.S133438
Kamibayashi, T., and Maze, M. (2000). Clinical uses of α2-adrenergic agonists. Anesthesiology 93, 1345–1349. doi: 10.1097/00000542-200011000-00030
Kapitza, K. P., Passie, T., Bernateck, M., and Karst, M. (2010). First non-contingent respiratory biofeedback placebo versus contingent biofeedback inpatients with chronic low back pain: a randomized, controlled, double-blind trial. Appl. Psychophysiol. Biofeedback 35, 207–217. doi: 10.1007/s10484-010-9130-1
Kato, Y., Kowalski, C. J., and Stohler, C. S. (2001). Habituation of the early pain-specific respiratory response in sustained pain. Pain 91, 57–63. doi: 10.1016/s0304-3959(00)00419-x
Killgore, W. D., Smith, R., Olson, E. A., Weber, M., Rauch, S. L., and Nickerson, L. D. (2017). Emotional intelligence is associated with connectivity within and between resting state networks. Soc. Cogn. Affect. Neurosci. 12, 1624–1636. doi: 10.1093/scan/nsx088
Kirchner, A., Birklein, F., Stefan, H., and Handwerker, H. O. (2000). Left vagus nerve stimulation suppresses experimentally induced pain. Neurology 55, 1167–1171. doi: 10.1212/wnl.55.8.1167
Kleiger, R. E., Stein, P. K., and Bigger, J. T. Jr. (2005). Heart rate variability: measurement and clinical utility. Ann. Noninvasive Electrocardiol. 10, 88–101. doi: 10.1111/j.1542-474x.2005.10101.x
Kniffin, T. C., Carlson, C. R., Ellzey, A., Eisenlohr-Moul, T., Beck, K. B., McDonald, R., et al. (2014). Using virtual reality to explore self-regulation in high-risk settings. Trauma Violence Abuse 15, 310–321. doi: 10.1177/1524838014521501
Koch, A., Zacharowski, K., Boehm, O., Stevens, M., Lipfert, P., Von Giesen, H. J., et al. (2007). Nitric oxide and pro-inflammatory cytokines correlate with pain intensity in chronic pain patients. Inflamm. Res. 56, 32–37. doi: 10.1007/s00011-007-6088-4
Kolacz, J., and Porges, S. W. (2018). Chronic diffuse pain and functional gastrointestinal disorders after traumatic stress: pathophysiology through a polyvagal perspective. Front. Med. 5:145. doi: 10.3389/fmed.2018.00145
Konnopka, A., Schaefert, R., Heinrich, S., Kaufmann, C., Luppa, M., Herzog, W., et al. (2012). Economics of medically unexplained symptoms: a systematic review of the literature. Psychother. Psychosom. 81, 265–275. doi: 10.1159/000337349
Kox, M., van Eijk, L. T., Zwaag, J., van den Wildenberg, J., Sweep, F. C., van der Hoeven, J. G., et al. (2014). Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc. Natl. Acad. Sci. U.S.A. 111, 7379–7384. doi: 10.1073/pnas.1322174111
Kraus, T., Hösl, K., Kiess, O., Schanze, A., Kornhuber, J., and Forster, C. (2007). BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J. Neural Transm. 114, 1485–1493. doi: 10.1007/s00702-007-0755-z
Kubin, L., Alheid, G. F., Zuperku, E. J., and McCrimmon, D. R. (2006). Central pathways of pulmonary and lower airway vagal afferents. J. Appl. Physiol. 101, 618–627. doi: 10.1152/japplphysiol.00252.2006
Kucyi, A., Salomons, T. V., and Davis, K. D. (2013). Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks. Proc. Natl. Acad. Sci. U.S.A. 110, 18692–18697. doi: 10.1073/pnas.1312902110
Laborde, S., Mosley, E., and Thayer, J. F. (2017). Heart rate variability and cardiac vagal tone in psychophysiological research–recommendations for experiment planning, data analysis, and data reporting. Front. Psychol. 8:213. doi: 10.3389/fpsyg.2017.00213
Lagos, L., Vaschillo, E., Vaschillo, B., Lehrer, P., Bates, M., and Pandina, R. (2008). Heart rate variability biofeedback as a strategy for dealing with competitive anxiety: a case study. Biofeedback 36:109.
Lange, G., Janal, M. N., Maniker, A., FitzGibbons, J., Fobler, M., Cook, D., et al. (2011). Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med. 12, 1406–1413. doi: 10.1111/j.1526-4637.2011.01203.x
Lee, J., Ellis, B., Price, C., and Baranowski, A. P. (2014). Chronic widespread pain, including fibromyalgia: a pathway for care developed by the british pain society. Br. J. Anaesth. 112, 16–24. doi: 10.1093/bja/aet351
Legrain, V., Van Damme, S., Eccleston, C., Davis, K. D., Seminowicz, D. A., and Crombez, G. A. (2009). neurocognitive model of attention to pain: behavioral and neuroimaging evidence. Pain 144, 230–232. doi: 10.1016/j.pain.2009.03.020
Lehrer, P. M. (2013). How does heart rate variability biofeedback work? resonance, the baroreflex, and other mechanisms. Biofeedback 41, 26–31. doi: 10.3389/fpsyg.2014.00756
Lehrer, P. M., Vaschillo, E., and Vaschillo, B. (2000). Resonant frequency biofeedback training to increase cardiac variability: rationale and manual for training. Appl. Psychophysiol. Biofeedback 25, 177–191.
Lehrer, P. M., Vaschillo, E., Vaschillo, B., Lu, S. E., Eckberg, D. L., Edelberg, R., et al. (2003). Heart rate variability biofeedback increases baroreflex gain and peak expiratory flow. Psychosom. Med. 65, 796–805. doi: 10.1097/01.psy.0000089200.81962.19
Leknes, S., Lee, M., Berna, C., Andersson, J., and Tracey, I. (2011). Relief as a reward: hedonic and neural responses to safety from pain. PLoS One 6:e17870. doi: 10.1371/journal.pone.0017870
Letzen, J. E., and Robinson, M. E. (2017). Negative mood influences default mode network functional connectivity in patients with chronic low back pain: implications for functional neuroimaging biomarkers. Pain 158, 48–57. doi: 10.1097/j.pain.0000000000000708
Lin, C. C., and Ward, S. E. (1996). Perceived self-efficacy and outcome expectancies in coping with chronic low back pain. Res. Nurs. Health 19, 299–310. doi: 10.1002/(sici)1098-240x(199608)19:4<299::aid-nur4>3.0.co;2-d
Loggia, M. L., Mogil, J. S., and Bushnell, M. C. (2008). Experimentally induced mood changes preferentially affect pain unpleasantness. J. Pain 9, 784–791. doi: 10.1016/j.jpain.2008.03.014
Lutz, A., Brefczynski-Lewis, J., Johnstone, T., and Davidson, R. J. (2008a). Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise. PLoS One 3:e1897. doi: 10.1371/journal.pone.0001897
Lutz, A., Slagter, H. A., Dunne, J. D., and Davidson, R. J. (2008b). Attention regulation and monitoring in meditation. Trends Cogn. Sci. 1, 163–169. doi: 10.1016/j.tics.2008.01.005
Maitre, B., Similowski, T., and Derenne, J. P. (1995). Physical examination of the adult patient with respiratory diseases: inspection and palpation. Eur. Respir. J. 8, 1584–1593.
Maletic, V., (2009). Neurobiology of depression, fibromyalgia and neuropathic pain. Front. Biosci. 14:5291–5338.
Mansfield, K. E., Sim, J., Croft, P., and Jordan, K. P. (2017). Identifying patients with chronic widespread pain in primary care. Pain 158:110. doi: 10.1097/j.pain.0000000000000733
Mansfield, K. E., Sim, J., Jordan, J. L., and Jordan, K. P. (2016). A systematic review and meta-analysis of the prevalence of chronic widespread pain in the general population. Pain 157, 55–64. doi: 10.1097/j.pain.0000000000000314
Mason, H., Vandoni, M., Debarbieri, G., Codrons, E., Ugargol, V., and Bernardi, L. (2013). Cardiovascular and respiratory effect of yogic slow breathing in the yoga beginner: what is the best approach? Evid. Based Complementary Altern. Med. 2013:743504. doi: 10.1155/2013/743504
Mayer, J. D., Roberts, R. D., and Barsade, S. G. (2008). Human abilities: emotional intelligence. Annu. Rev. Psychol. 59, 507–536.
Mayer, T. G., Towns, B. L., Neblett, R., Theodore, B. R., and Gatchel, R. J. (2008). Chronic widespread pain in patients with occupational spinal disorders: prevalence, psychiatric comorbidity, and association with outcomes. Spine 33, 1889–1897. doi: 10.1097/BRS.0b013e3181808c4e
McCraty, R., and Childre, D. (2010). Coherence: bridging personal, social, and global health. Altern. Ther. Health Med. 16, 10–24.
McCraty, R., and Shaffer, F. (2015). Heart rate variability: new perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Glob. Adv. Health Med. 4, 46–61. doi: 10.7453/gahmj.2014.073
Mehling, W. E., Hamel, K. A., Acree, M., Byl, N., and Hecht, F. M. (2005). Randomized, controlled trial of breath therapy for patients with chronic low-back pain. Altern. Ther. Health Med. 11:44.
Meller, T., Stiehm, F., Malinowski, R., and Thieme, K. (2016). Baroreflex sensitivity and chronic pain: pathogenetic significance and clinical implications. Schmerz 30, 470–476.
Meregnani, J., Clarençon, D., Vivier, M., Peinnequin, A., Mouret, C., Sinniger, V., et al. (2011). Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease. Auton. Neurosci. 160, 82–89. doi: 10.1016/j.autneu.2010.10.007
Mohammed, A. R., and Mohammed, N. S. (2014). Effect of breathing exercise on respiratory efficiency and pain intensity among children receiving chemotherapy. J. Educ. Pract. 5:6.
Moore, A. W., Gruber, T., Derose, J., and Malinowski, P. (2012). Regular, brief mindfulness meditation practice improves electrophysiological markers of attentional control. Front. Hum. Neurosci. 6:18. doi: 10.3389/fnhum.2012.00018
Morley, S., Eccleston, C., and Williams, A. (1999). Systematic review and meta-analysis of randomized controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain 80, 1–3.
Morris, G. L., and Mueller, W. M. (1999). Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. Neurology 53:1731. doi: 10.1212/wnl.53.8.1731
Mose, S., Christiansen, D. H., Jensen, J. C., and Andersen, J. H. (2016). Widespread pain–do pain intensity and care-seeking influence sickness absence?–A population-based cohort study. BMC Musculoskelet. Disord. 17:197. doi: 10.1186/s12891-016-1056-1
Moslehi, M., Samouei, R., Tayebani, T., and Kolahduz, S. (2015). A study of the academic performance of medical students in the comprehensive examination of the basic sciences according to the indices of emotional intelligence and educational status. J. Educ. Health Promot. 4:66. doi: 10.4103/2277-9531.162387
Mukai, S., and Hayano, J. (1995). Heart rate and blood pressure variabilities during graded head-up tilt. J. Appl. Physiol. 78, 212–216. doi: 10.1152/jappl.1995.78.1.212
Nahman-Averbuch, H., Sprecher, E., Jacob, G., and Yarnitsky, D. (2016). The relationships between parasympathetic function and pain perception: the role of anxiety. Pain Pract. 16, 1064–1072. doi: 10.1111/papr.12407
Napadow, V., Kim, J., Clauw, D. J., and Harris, R. E. (2012). Brief report: decreased intrinsic brain connectivity is associated with reduced clinical pain in fibromyalgia. Arthritis Rheumatol. 64, 2398–2403. doi: 10.1002/art.34412
National Academies of Sciences, Engineering and Medicine (2017). Pain Management and the Opioid Epidemic: Balancing Societal and Individual Benefits and Risks of Prescription Opioid Use. Washington, DC: National Academies Press.
Navratilova, E., and Porreca, F. (2014). Reward and motivation in pain and pain relief. Nat. Neurosci. 17:1304. doi: 10.1038/nn.3811
Nesvold, A., Fagerland, M. W., Davanger, S., Ellingsen, Ø, Solberg, E. E., Holen, A., et al. (2012). Increased heart rate variability during nondirective meditation. Eur. J. Prev. Cardiol. 19, 773–780. doi: 10.1177/1741826711414625
Nishino, T., Shimoyama, N., Ide, T., and Isono, S. (1999). Experimental pain augmentsexperimental dyspnea, but not vice versa in human volunteers. Anesthesiology 91, 1633–1638.
Ong, A. D., Zautra, A. J., and Reid, M. C. (2010). Psychological resilience predicts decreases in pain catastrophizing through positive emotions. Psychol. Aging 25, 516–523. doi: 10.1037/a0019384
Ottaviani, C., Shapiro, D., and Couyoumdjian, A. (2013). Flexibility as the key for somatic health: from mind wandering to perseverative cognition. Biol. Psychol. 94, 38–43. doi: 10.1016/j.biopsycho.2013.05.003
Pacheco-López, G., Engler, H., Niemi, M. B., and Schedlowski, M. (2006). Expectations and associations that heal: immunomodulatory placebo effects and its neurobiology. Brain Behav. Immun. 20, 430–446. doi: 10.1016/j.bbi.2006.05.003
Pal, G. K., and Velkumary, S. (2004). Effect of short-term practice of breathing exercises on autonomic functions in normal human volunteers. Indian J. Med. Res. 120:115. doi: 10.1007/bf01826206
Park, E., Oh, H., and Kim, T. (2013). The effects of relaxation breathing on procedural pain and anxiety during burn care. Burns 39, 1101–1106. doi: 10.1016/j.burns.2013.01.006
Pavithran, P., Nandeesha, H., Sathiyapriya, V., Bobby, Z., and Madanmohan, T. (2008). Short-term heart variability and oxidative stress in newly diagnosed essential hypertension. Clin. Exp. Hypertens 30, 486–496. doi: 10.1080/10641960802251875
Perlitz, V., Lambertz, M., Cotuk, B., Grebe, R., Vandenhouten, R., Flatten, G., et al. (2004). Cardiovascular rhythms in the 0.15-Hz band: common origin of identical phenomena in man and dog in the reticular formation of the brain stem? Pflügers Arch. 448, 579–591. doi: 10.1007/s00424-004-1291-4
Perri, M. A., and Halford, E. (2004). Pain and faulty breathing: a pilot study. J. Bodyw. Mov. Ther. 8, 297–306. doi: 10.1016/s1360-8592(03)00085-8
Peuker, E. T., and Filler, T. J. (2002). The nerve supply of the human auricle. Clin. Anat. 15, 35–37. doi: 10.1002/ca.1089
Picavet, H. S., Vlaeyen, J. W., and Schouten, J. S. (2002). Pain catastrophizing and kinesiophobia: predictors of chronic low back pain. Am. J. Epidemiol. 156, 1028–1034. doi: 10.1093/aje/kwf136
Pittig, A., Arch, J. J., Lam, C. W., and Craske, M. G. (2013). Heart rate and heart rate variability in panic, social anxiety, obsessive–compulsive, and generalized anxiety disorders at baseline and in response to relaxation and hyperventilation. Int. J. Psychophysiol. 87, 19–27. doi: 10.1016/j.ijpsycho.2012.10.012
Porges, S. W. (2009). The polyvagal theory: new insights into adaptive reactions of the autonomic nervous system. Cleve. Clin. J. Med. 76(Suppl. 2), S86. doi: 10.3949/ccjm.76.s2.17
Quintana, D. S., Alvares, G. A., and Heathers, J. A. (2016). Guidelines for reporting articles on psychiatry and heart rate variability (GRAPH): recommendations to advance research communication. Transl. Psychiatry 6:e803. doi: 10.1038/tp.2016.73
Raghuraj, P., Ramakrishnan, A. G., Nagendra, H. R., and Telles, S. (1998). Effect of two selected yogic breathing techniques on heart rate variability. Indian J. Physiol. Pharmacol. 42, 467–472.
Raichle, M. E., MacLeod, A. M., Snyder, A. Z., Powers, W. J., Gusnard, D. A., and Shulman, G. L. (2001). A default mode of brain function. Proc. Natl. Acad. Sci. U.S.A. 98, 676–682.
Ramírez-Maestre, C., Esteve, R., and López, A. E. (2012). The role of optimism and pessimism in chronic pain patients adjustment. Span. J. Psychol. 15, 286–294. doi: 10.5209/rev_sjop.2012.v15.n1.37335
Randich, A., and Gebhart, G. F. (1992). Vagal afferent modulation of nociception. Brain Res. Rev. 17, 77–99. doi: 10.1016/0165-0173(92)90009-b
Ren, K., Randich, A., and Gebhart, G. F. (1988). Vagal afferent modulation of a nociceptive reflex in rats: involvement of spinal opioid and monoamine receptors. Brain Res. 446, 285–294. doi: 10.1016/0006-8993(88)90887-6
Ren, K., Zhuo, M., Randich, A., and Gebhart, G. F. (1993). Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats. J. Neurophysiol. 69, 1530–1540. doi: 10.1152/jn.1993.69.5.1530
Russell, M. E., Hoffman, B., Stromberg, S., and Carlson, C. R. (2014). Use of controlled diaphragmatic breathing for the management of motion sickness in a virtual reality environment. Appl. Psychophysiol. Biofeedback 39, 269–277. doi: 10.1007/s10484-014-9265-6
Russell, M. E., Scott, A. B., Boggero, I. A., and Carlson, C. R. (2017). Inclusion of a rest period in diaphragmatic breathing increases high frequency heart rate variability: implications for behavioral therapy. Psychophysiology 54, 358–365. doi: 10.1111/psyp.12791
Schanberg, L. E., Sandstrom, M. J., Starr, K., Gil, K. M., Lefebvre, J. C., Keefe, F. J., et al. (2000). The relationship of daily mood and stressful events to symptoms in juvenile rheumatic disease. Arthritis Care Res. 13, 33–41. doi: 10.1002/1529-0131(200002)13:1<33::aid-art6>3.0.co;2-s
Seth, A. K. (2013). Interoceptive inference, emotion, and the embodied self. Trends Cogn. Sci. 17, 565–573. doi: 10.1016/j.tics.2013.09.007
Seth, A. K., and Friston, K. J. (2016). Active interoceptive inference and the emotional brain. Philos. Trans. R. Soc. B 371:20160007. doi: 10.1098/rstb.2016.0007
Shannahoff-Khalsa, D. S., and Kennedy, B. (1993). The effects of unilateral forced nostril breathing on the heart. Int. J. Neurosci. 73, 47–60. doi: 10.3109/00207459308987210
Simons, L. E., Elman, I., and Borsook, D. (2014). Psychological processing in chronic pain: a neural systems approach. Neurosci. Biobehav. Rev. 39, 61–78. doi: 10.1016/j.neubiorev.2013.12.006
Smith, M. D., Russell, A., and Hodges, P. W. (2006). Disorders of breathing and continence have a stronger association with back pain than obesity and physical activity. Aust. J. Physiother. 52, 11–16. doi: 10.1016/s0004-9514(06)70057-5
Sommer, C., Häuser, W., Gerhold, K., Joraschky, P., Petzke, F., Tölle, T., et al. (2008). Etiology and pathophysiology of fibromyalgia syndrome and chronic widespread pain. Schmerz 22, 267–282. doi: 10.1007/s00482-008-0672-6
Sood, A., and Jones, D. T. (2013). On mind wandering, attention, brain networks, and meditation. Explore 9, 136–141. doi: 10.1016/j.explore.2013.02.005
Stancák, J. A., Kuna, M., Dostalek, C., and Vishnudevananda, S. (1991a). Kapalabhati–yogic cleansing exercise. II. EEG topography analysis. Homeost. Health Dis. 33, 182–189.
Stancák, J. A., Kuna, M., Vishnudevananda, S., and Dostalek, C. (1991b). Kapalabhati–yogic cleansing exercise. I. Cardiovascular and respiratory changes. Homeost. Health Dis. 33, 126–134.
Stancák, J. A., Pfeffer, D., Hrudová, L., Sovka, P., and Dostálek, C. (1993). Electroencephalographic correlates of paced breathing. Neuroreport 4, 723–726. doi: 10.1097/00001756-199306000-00031
Steffen, P. R., Austin, T., DeBarros, A., and Brown, T. (2017). The impact of resonance frequency breathing on measures of heart rate variability, blood pressure, and mood. Front. Public Health 5:222. doi: 10.3389/fpubh.2017.00222
Stein, P. K., and Pu, Y. (2012). Heart rate variability, sleep and sleep disorders. Sleep Med. Rev. 16, 47–66. doi: 10.1016/j.smrv.2011.02.005
Stetter, F., and Kupper, S. (2002). Autogenic training: a meta-analysis of clinical outcome studies. Appl. Psychophysiol. Biofeedback 27, 45–98.
Strauss-Blasche, G., Moser, M., Voica, M., McLeod, D. R., Klammer, N., and Marktl, W. (2000). Relative timing of inspiration and expiration affects respiratory sinus arrhythmia. Clin. Exp. Pharmacol. Physiol. 27, 601–606. doi: 10.1046/j.1440-1681.2000.03306.x
Sturgeon, J. A., and Zautra, A. J. (2010). Resilience: a new paradigm for adaptation to chronic pain. Curr. Pain Headache Rep. 14, 105–112. doi: 10.1007/s11916-010-0095-9
Su, I. W., Wu, F. W., Liang, K. C., Cheng, K. Y., Hsieh, S. T., Sun, W. Z., et al. (2016). Pain perception can be modulated by mindfulness training: a resting-state fMRI study. Front. Hum. Neurosci. 10:570. doi: 10.3389/fnhum.2016.00570
Subramanian, H. H., and Holstege, G. (2010). Periaqueductal gray control of breathing. in New Frontiers in Respiratory Control eds I. Homma, Y. Fukuchi, H. Onimaru (New York, NY: Springer), 353–358. doi: 10.1007/978-1-4419-5692-7_72
Sullivan, M. D., Edlund, M. J., Fan, M. Y., DeVries, A., Braden, J. B., and Martin, B. C. (2008). Trends in use of opioids for non-cancer pain conditions 2000–2005 in commercial and medicaid insurance plans: the TROUP study. Pain 138, 440–449. doi: 10.1016/j.pain.2008.04.027
Sullivan, M. J., Bishop, S. R., and Pivik, J. (1995). The pain catastrophizing scale: development and validation. Psychol. Assess. 7, 524–532. doi: 10.1037//1040-3590.7.4.524
Sullivan, M. J., Rodgers, W. M., and Kirsch, I. (2001a). Catastrophizing, depression and expectancies for pain and emotional distress. Pain 91, 147–154. doi: 10.1016/s0304-3959(00)00430-9
Sullivan, M. J., Thorn, B., Haythornthwaite, J. A., Keefe, F., Martin, M., Bradley, L. A., et al. (2001b). Theoretical perspectives on the relation between catastrophizing and pain. Clin. J. Pain 17, 52–64. doi: 10.1097/00002508-200103000-00008
Tarapacki, J. A., Thompson, A. C., and Kristal, M. B. (1992). Gastric vagotomy blocks opioid analgesia enhancement produced by placenta ingestion. Physiol. Behav. 52, 179–182. doi: 10.1016/0031-9384(92)90449-c
Tateishi, Y., Oda, S., Nakamura, M., Watanabe, K., Kuwaki, T., Moriguchi, T., et al. (2007). Depressed heart rate variability is associated with high IL-6 blood level and decline in the blood pressure in septic patients. Shock 28, 549–553. doi: 10.1097/shk.0b013e3180638d1
Telles, S., Sharma, S. K., Gupta, R. K., Bhardwaj, A. K., and Balkrishna, A. (2016). Heart rate variability in chronic low back pain patients randomized to yoga or standard care. BMC Complementary Altern. Med. 16:279. doi: 10.1186/s12906-016-1271-1
Thayer, J. F. (2007). What the heart says to the brain (and vice versa) and why we should listen. Psihologijske Teme 16, 241–250.
Thayer, J. F. (2009). Heart rate variability: a neurovisceral integration model. Encycl. Neurosci. 2009, 1041–1047. doi: 10.1016/b978-008045046-9.01991-4
Thayer, J. F., Hansen, A. L., Saus-Rose, E., and Johnsen, B. H. (2009). Heart rate variability, prefrontal neural function, and cognitive performance: the neurovisceral integration perspective on self-regulation, adaptation, and health. Ann. Behav. Med. 37, 141–153. doi: 10.1007/s12160-009-9101-z
Thayer, J. F., and Lane, R. D. (2000). A model of neurovisceral integration in emotion regulation and dysregulation. J. Affect. Disord. 61, 201–216. doi: 10.1016/s0165-0327(00)00338-4
Tracey, I. (2010). Getting the pain you expect: mechanisms of placebo, nocebo and reappraisal effects in humans. Nat. Med. 16, 1277–1283. doi: 10.1038/nm.2229
Treede, R. D., Rief, W., Barke, A., Aziz, Q., Bennett, M. I., Benoliel, R., et al. (2015). A classification of chronic pain for ICD-11. Pain 156, 1003–1007.
Triedman, J. K., and Saul, J. P. (1994). Blood pressure modulation by central venous pressure and respiration. Buffering effects of the heart rate reflexes. Circulation 89, 169–179. doi: 10.1161/01.cir.89.1.169
Turk, D. C., and Rudy, T. E. (1992). Cognitive factors and persistent pain: a glimpse into pandora’s box. Cogn. Ther. Res. 16, 99–122. doi: 10.1007/bf01173484
Turk, D. C., Wilson, H. D., and Cahana, A. (2011). Treatment of chronic non-cancer pain. Lancet 377, 2226–2235. doi: 10.1016/S0140-6736(11)60402-9
Turner, J. A., Shortreed, S. M., Saunders, K. W., LeResche, L., Thielke, S., and Von Korff, M. (2016). Does association of opioid use with pain and function differ by fibromyalgia or widespread pain status? Pain 157, 2208–2216. doi: 10.1097/j.pain.0000000000000631
van Middendorp, H., Kox, M., Pickkers, P., and Evers, A. W. (2016). The role of outcome expectancies for a training program consisting of meditation, breathing exercises, and cold exposure on the response to endotoxin administration: a proof-of-principle study. Clin. Rheumatol. 35, 1081–1085. doi: 10.1007/s10067-015-3009-8
Vaschillo, E., Lehrer, P., Rishe, N., and Konstantinov, M. (2002). Heart rate variability biofeedback as a method for assessing baroreflex function: a preliminary study of resonance in the cardiovascular system. Appl. Psychophysiol. Biofeedback 27, 1–27. doi: 10.1023/A:1014587304314
Veehof, M. M., Oskam, M. J., Schreurs, K. M., and Bohlmeijer, E. T. (2011). Acceptance-based interventions for the treatment of chronic pain: a systematic review and meta-analysis. Pain 152, 533–542. doi: 10.1016/j.pain.2010.11.002
Viane, I., Crombez, G., Eccleston, C., Devulder, J., and De Corte, W. (2004). Acceptance of the unpleasant reality of chronic pain: effects upon attention to pain and engagement with daily activities. Pain 112, 282–288. doi: 10.1016/j.pain.2004.09.008
Villemure, C., and Bushnell, M. C. (2009). Mood influences supraspinal pain processing separately from attention. J. Neurosci. 29, 705–715. doi: 10.1523/JNEUROSCI.3822-08.2009
Villemure, C., Slotnick, B. M., and Bushnell, M. C. (2003). Effects of odors on pain perception: deciphering the roles of emotion and attention. Pain 106, 101–108. doi: 10.1016/s0304-3959(03)00297-5
Vonck, K., Raedt, R., Naulaerts, J., De Vogelaere, F., Thiery, E., Van Roost, D., et al. (2014). Vagus nerve stimulation… 25 years later! What do we know about the effects on cognition? Neurosci. Biobehav. Rev. 45, 63–71. doi: 10.1016/j.neubiorev.2014.05.005
Vos, T., Flaxman, A. D., Naghavi, M., Lozano, R., Michaud, C., Ezzati, M., et al. (2013). Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet 380, 2163–2196. doi: 10.1016/S0140-6736(12)61729-2
Wiech, K., and Tracey, I. (2009). The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 47, 987–994. doi: 10.1016/j.neuroimage.2009.05.059
Wiech, K., and Tracey, I. (2013). Pain, decisions, and actions: a motivational perspective. Front. Neurosci. 7:46. doi: 10.3389/fnins.2013.00046
Williams, A. C., Eccleston, C., and Morley, S. (2012). Psychological Therapies for the Management of Chronic Pain (Excluding Headache) in Adults. London: The cochrane library.
World Health Organization (2018). Groups that Were Involved in ICD-11 Revision. Geneva: World Health Organization.
Xu, J., Vik, A., Groote, I. R., Lagopoulos, J., Holen, A., Ellingsen, Ø, et al. (2014). Nondirective meditation activates default mode network and areas associated with memory retrieval and emotional processing. Front. Hum. Neurosci. 8:86. doi: 10.3389/fnhum.2014.00086
Younger, J., McCue, R., and Mackey, S. (2009). Pain outcomes: a brief review of instruments and techniques. Curr. Pain Headache Rep. 13, 39–43. doi: 10.1007/s11916-009-0009-x
Yuan, H., and Silberstein, S. D. (2016). Vagus nerve and vagus nerve stimulation, a comprehensive review: part II. Headache 56, 259–266. doi: 10.1111/head.12650
Zaki, J., Davis, J. I., and Ochsner, K. N. (2012). Overlapping activity in anterior insula during interoception and emotional experience. Neuroimage 62, 493–499. doi: 10.1016/j.neuroimage.2012.05.012
Zautra, A. J., Fasman, R., Davis, M. C., and Arthur, D. (2010). The effects of slow breathing on affective responses to pain stimuli: an experimental study. Pain 149, 12–18. doi: 10.1016/j.pain.2009.10.001
Zautra, A. J., Johnson, L. M., and Davis, M. C. (2005). Positive affect as a source of resilience for women in chronic pain. J. Consult. Clin. Psychol. 73:212. doi: 10.1037/0022-006x.73.2.212
Zeng, X., Chio, F., Oei, T., Leung, F., and Liu, X. (2017). A systematic review of associations between amount of meditation practice and outcomes in interventions using the four immeasurables meditations. Front. Psychol. 8:141. doi: 10.3389/fpsyg.2017.00141
Keywords: chronic widespread pain, non-directive meditation, diaphragmatic breathing, transcutaneous vagal nerve stimulation, baroreceptor sensitivity, heart rate variability, resonance frequency breathing, motivation
Citation: Paccione CE and Jacobsen HB (2019) Motivational Non-directive Resonance Breathing as a Treatment for Chronic Widespread Pain. Front. Psychol. 10:1207. doi: 10.3389/fpsyg.2019.01207
Received: 19 November 2018; Accepted: 07 May 2019;
Published: 11 June 2019.
Edited by:
Gianluca Castelnuovo, Catholic University of the Sacred Heart, ItalyCopyright © 2019 Paccione and Jacobsen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Charles Ethan Paccione, charles.ethan.paccione@columbia.edu