We are pleased to introduce the collection Frontiers in Pain Research – Highlights in Abdominal and Pelvic Pain 2021/22. This collection will welcome and showcase a selection of high impact articles authored by leaders in the field. The work presented here highlights the broad diversity of research performed across the Abdominal and Pelvic Pain section, and aims to put a spotlight on the main areas of interest. This collection aims to further support Frontiers’ strong community by shining a spotlight on our authors' highly impactful research.

Jiading Branch of Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

The University of Manchester

Flinders University

Discover the diverse range of research around Abdominal and Pelvic Pain with Frontiers' latest collection.

. This research topic explores the effects of various treatments on chronic visceral pain. It has been found that: <ul> <li>48.3% of IBS patients had detailed memories of the events surrounding their symptom onset, which was associated with greater symptom severity, higher anxiety/depression, and poorer HRQOL.</li> <li>40% of endometriosis patients experienced neuropathic-like pain, which was associated with higher pain intensities, greater psychological distress, and cognitive impairment.</li> <li>VSL#3 probiotic treatment for 4 or 8 weeks had a positive effect on abdominal pain, stooling, gut permeability, microbiome composition and function in adults with IBS.</li> <li>Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain.</li> </ul>

Views

Article Views

Article Downloads

Frontiers in Pain Research

Abdominal and Pelvic Pain

Highlights in Abdominal and Pelvic Pain 2021/22

Editorial on the Research Topic <a href="https://www.frontiersin.org/research-topics/32684/highlights-in-abdominal-and-pelvic-pain-202122">Highlights in abdominal and pelvic pain 2021/2022</a>It is our great pleasure to organize this Research Topic in Frontiers in Pain Research: Highlights in Abdominal and Pelvic Pain 2021/22. This Research Topic has a selection of high-impact articles authored by four groups of excellent international leaders in the field of pain research and has shared varied theories and/or experiences in the clinical treatment and therapy of abdominal and pelvic pain research. The work presented here highlights the broad diversity of research carried out in the abdominal and pelvic pain section, not specifically limited to years, and aims to highlight the main areas of interest among many clinical departments: anesthesiology and pain medicine, neurology, obstetrics and gynecology, urology, gastroenterology, immunology and allergy, surgery and orthopedics, and general medicine. Of course, state-of-the-art concepts, such as the brain-gut axis, or vice versa, also exist in some research collection papers (<a href="#B1">1</a>, <a href="#B2">2</a>).The first review article, Importance of Non-pharmacological Approaches for Treating Irritable Bowel Syndrome: Mechanisms and Clinical Relevance by <a href="https://doi.org/10.3389/fpain.2020.609292">Orock et al.</a>, introduced the updated situation on chronic visceral pain that represents an important unmet clinical need, with the severity of pain preventing individuals from participating in day-to-day activities and negatively affecting their quality of life. Although chronic visceral pain can be multifactorial, with many different biological and psychological systems that contribute to the onset and severity of symptoms, the main trigger is exposure to emotional and physical irritation, especially gastrointestinal disorders (GI) such as irritable bowel syndrome (IBS). To date, pharmacological treatments for patients with chronic visceral pain generally lack efficacy and are fraught with unwanted side effects. Cognitive behavioral therapy has emerged as a psychotherapy that shows efficacy in ameliorating stress-induced chronic visceral pain. It is interesting to read these articles on acupuncture mechanism disputes for disorders of the digestive system and the potential cellular mechanism (<a href="#B3">3</a>, <a href="#B4">4</a>). Clinical acupuncture trials on the efficacy of treating symptoms of IBS have not yet reached a consensus; however, clinical efforts have been confirmed to reduce pain perception in patients. Experimental studies in rats identified that neurogenic inflammatory spots corresponded to acupuncture points in patients.The second article, a wonderfully novel article about probiotic organisms identified in stool that were significantly correlated with improvement in colonic permeability and clinical symptoms, led future studies to investigate the mechanistic roles of VSL#3 and colonic permeability in the pathophysiology of IBS in a larger randomized controlled trial (submitted by <a href="https://doi.org/10.3389/fpain.2021.691689">Boonma et al.</a>). It is well known that IBS is more common in children than in adults and that it affects the quality of human life. Once considered a disorder caused by abnormalities in gut smooth muscle, visceral hypersensitivity, and/or central nervous system hypervigilance, a change in focus has been observed to include both central and peripheral mechanisms in pathophysiology in the past decade. Related peripheral mechanisms include abnormal colonic transit and rectal evacuation, intraluminal intestinal irritants, altered gut microbiome, and enteroendocrine cell dysfunction. The United States Food and Drug Administration approved the authors to conduct a thorough safety study of VSL#3 in adults with IBS before its use in a randomized study in children with IBS. The researchers used this opportunity to investigate adult patients with IBS with matched fecal omics data and the effects of two dosing durations of VSL#3 on gut permeability, recovery of probiotic organisms, and changes in gut microbiome composition determined by shotgun metagenomic sequencing, as well as alterations in metabolome profile (bile acid). The results of the RCT suggested that the probiotic organisms identified in the stool were significantly correlated with improved colonic permeability and clinical symptoms.The third article, Is There a Neuropathic-Like Component to Endometriosis-Associated Pain? Results From a Large Cohort Questionnaire Study by <a href="https://doi.org/10.3389/fpain.2021.743812">Coxon et al.</a>, reported that clinical data indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of females. Although further investigation is required, these findings challenge the current conceptualization of endometriosis-associated pain as nociceptive, and the authors advocate for a new perspective on this type of pain. Even within gynecology, related visceral pain probably also results mainly from the neuropathic-like factor (<a href="#B5">5</a>, <a href="#B6">6</a>).The fourth article, wonderfully related to the psychological gut brain axis, is by <a href="https://doi.org/10.3389/fpain.2022.892313">Sayuk et al.</a>, entitled Episodic Memories Among Irritable Bowel Syndrome Patients: An Important Aspect of the IBS Symptom Experience. They identified that 14/29 (48.3%) IBS subjects reported episodic memories of the onset of IBS symptoms, often GI infections/enteritis (35.7%). Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer health-related quality of life (HRQOL). However, the subtest memory specificity was not different based on episodic memory. Patients with IBS often reported episodic memory associated with the onset of symptoms, and this recall appears to be associated with more severe symptoms. To date, the much discussed concept of intestinal microflora has been described for the special scientific mechanism; more recently, the main flow mechanism of the nervous and mental axis plays a substantially key role (<a href="#B1">1</a>). In fact, the nature of abnormal nervous and mental activities should inspire many researchers to make concerted efforts in the treatment of abdominal and pelvic pain and the related interactions.Both authors contributed to the article and approved the submitted version.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Highlights in abdominal and pelvic pain 2021/2022

Objective:Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset (“episodic memories”). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.</sec>MethodsReferral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories.</sec>Results14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories.</sec>ConclusionsIBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.</sec>

Objective: Some IBS patients possess detailed memories of the events surrounding their bowel symptom onset (“episodic memories”). In this exploratory study we sought to: (1) examine memory relationship with gastrointestinal (GI) symptom severity, extraintestinal symptoms, and mood; (2) qualitatively explore memory valence and content in IBS patients with or without episodic memories.Methods: Referral IBS patients n = 29; age 47.0± 2.2 years, 79.3% female) enrolled in this cross-sectional, mixed methods research study. Participants completed validated specific memory instruments [Autobiographical Memory Test (AMT), Sentence Completion for Events from the Past Test (SCEPT)] and relevant questionnaires [IBS symptoms 10-cm visual analog scale); SF-36 Health-related quality of life (HRQOL); Perley-Guze and PHQ-15/12: somatization; Beck Depression/Anxiety Inventories). Qualitative analysis examined the content and valence of general memories.Results: 14/29 (48.3%) of IBS subjects endorsed episodic memories of IBS symptom onset, often GI infections/enteritis (35.7%). Recall of the exact year (69%) and month (60%) of symptom onset were common. Episodic memories were associated with greater IBS symptom severity/bother, higher anxiety/depression, and poorer HRQOL. Though AMT and SCEPT memory specificity were not different based on episodic memories, overgeneralization to negatively-valenced cues in the AMT was associated with more severe IBS in those without episodic memory. Qualitative analysis revealed no observable differences in topic focus of IBS patients with and without episodic memories.Conclusions: IBS patients often endorse episodic memories associated with symptom onset, and this recall seems to associate with more severe symptoms. Overgeneralization responses to negative stimuli may lead to worse bowel symptoms in those without episodic memories. IBS memory specificity may associate with qualitative differences in processing psychosocial experiences and might be important to IBS pathophysiology.

Episodic Memories Among Irritable Bowel Syndrome (IBS) Patients: An Important Aspect of the IBS Symptom Experience

Background: Pain is one of the primary symptoms of endometriosis, a chronic inflammatory condition characterised by the presence of endometrial tissue outside the uterus. Endometriosis-associated pain is commonly considered as nociceptive in nature, but its clinical presentation suggests that it might have neuropathic-like properties in a subgroup of patients.Methods: This is a cross sectional study using an online survey. The survey was distributed by patient support websites. The survey was composed of validated questionnaires assessing pain symptoms, psychological measures and questions about number of surgeries.Main Results: We had 1,417 responses which met the inclusion criteria. Using standard painDETECT cut-off scores, we found that pain was classified as neuropathic in 40% of patients and as mixed neuropathic/nociceptive in a further 35%. In line with observations in other neuropathic conditions, the neuropathic subgroup reported higher pain intensities, greater psychological distress and cognitive impairment. Neuropathic pain was also more likely in those with more surgeries to the abdomen and a longer history of pain. As revealed by a cluster analysis, those with a neuropathic pain component could further be divided into two subgroups based on their sensory profile.Conclusions: The data presented here indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of women. Although further investigation is required, our finding challenges the current conceptualisation of endometriosis-associated pain as nociceptive and advocates for a new perspective on this type of pain, which is so debilitating to a large number of women.

Background: Pain is one of the primary symptoms of endometriosis, a chronic inflammatory condition characterised by the presence of endometrial tissue outside the uterus. Endometriosis-associated pain is commonly considered as nociceptive in nature, but its clinical presentation suggests that it might have neuropathic-like properties in a subgroup of patients.Methods: This is a cross sectional study using an online survey. The survey was distributed by patient support websites. The survey was composed of validated questionnaires assessing pain symptoms, psychological measures and questions about number of surgeries.Main Results: We had 1,417 responses which met the inclusion criteria. Using standard painDETECT cut-off scores, we found that pain was classified as neuropathic in 40% of patients and as mixed neuropathic/nociceptive in a further 35%. In line with observations in other neuropathic conditions, the neuropathic subgroup reported higher pain intensities, greater psychological distress and cognitive impairment. Neuropathic pain was also more likely in those with more surgeries to the abdomen and a longer history of pain. As revealed by a cluster analysis, those with a neuropathic pain component could further be divided into two subgroups based on their sensory profile.Conclusions: The data presented here indicate that endometriosis-associated pain includes a neuropathic-like component in a substantial proportion of women. Although further investigation is required, our finding challenges the current conceptualisation of endometriosis-associated pain as nociceptive and advocates for a new perspective on this type of pain, which is so debilitating to a large number of women.

Is There a Neuropathic-Like Component to Endometriosis-Associated Pain? Results From a Large Cohort Questionnaire Study

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment.Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial.Clinical Trial Registration:<ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">www.clinicaltrials.gov</ext-link>, Identifier: NCT00971711.

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment.Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial.Clinical Trial Registration: <a href="http://www.clinicaltrials.gov" style="color:grey;">www.clinicaltrials.gov</a>, Identifier: NCT00971711.

Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome

Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.

Chronic visceral pain represents a major unmet clinical need with the severity of pain ranging from mild to so severe as to prevent individuals from participating in day-to-day activities and detrimentally affecting their quality of life. Although chronic visceral pain can be multifactorial with many different biological and psychological systems contributing to the onset and severity of symptoms, one of the major triggers for visceral pain is the exposure to emotional and physical stress. Chronic visceral pain that is worsened by stress is a hallmark feature of functional gastrointestinal disorders such as irritable bowel syndrome (IBS). Current pharmacological interventions for patients with chronic visceral pain generally lack efficacy and many are fraught with unwanted side effects. Cognitive behavioral therapy (CBT) has emerged as a psychotherapy that shows efficacy at ameliorating stress-induced chronic visceral pain; however, the molecular mechanisms underlying CBT remain incompletely understood. Preclinical studies in experimental models of stress-induced visceral pain employing environmental enrichment (EE) as an animal model surrogate for CBT are unraveling the mechanism by which environmental signals can lead to long-lasting changes in gene expression and behavior. Evidence suggests that EE signaling interacts with stress and nociceptive signaling. This review will (1) critically evaluate the behavioral and molecular changes that lead to chronic pain in IBS, (2) summarize the pharmacological and non-pharmacological approaches used to treat IBS patients, and (3) provide experimental evidence supporting the potential mechanisms by which CBT ameliorates stress-induced visceral pain.