About this Research Topic

Background

In the past decades, muscle pain has posed a big challenge in exercise medicine. This is specifically apparent when treating high-performance athletes and physically active individuals, as well as older individuals and for those who experience chronic pain. Diffuse exercise-related muscle pain, focal/multifocal and at rest myalgia, often respond poorly to the current available drug therapies. Another major concern is that aging- and disease-related physiological changes, coupled with the deleterious effects of physical inactivity and related comorbidities, negatively impact the process of initiating and maintaining physical activity. The mitigation of the aforementioned can improve overall health and physical independence of older adults.

New emerging and exciting areas in this field are investigating into the modulation of immune cell-mediated muscle nociceptor sensitization during overuse and myocyte injury. The exaggerated activation of leukocytes in response to injuries or persistence of noxious stimuli, results in the release of inflammatory mediators including cytokines, chemokines and free radicals, which can contribute to inflammation, pain, and ultimately cell damage. These mediators can alter several intrinsic signaling pathways that regulate inflammation in myocytes. The modulation of the activation of NFκB, PCG-1α, and myogenesis-related factors, for example, has been implicated in muscle damage and death, atrophy, and metabolic disorders. NFκB downstream cytokine TNF-α may shatter the differentiation of mature myocyte, inducing protein degradation and cachexia. On the other hand, the activation of protein kinases and ion channels in muscle nociceptors in response to exercise or muscle injury, also contribute to muscle pain.

Interestingly, physical training under professional supervision has shown to induce analgesia in patients with chronic inflammatory diseases, through mechanisms involving the participation of anti-inflammatory macrophages for example. Therefore, further studies focusing on the pharmacology of these analgesic mechanisms are warranted as there is still an urgent need for novel efficacious therapies with fewer adverse effects for exercise-related pain, as well as muscle inflammation and other pain conditions. These novel therapies have the potential of significantly improving therapy options for a wide array of patients, as well aiding preventive and therapeutic care in age-related diseases by permitting increased physical activity.

In this sense, this Research Topic is intended to form a compilation of papers regarding novel advances in pharmacological targeting of leukocytes and its products in the context of muscle inflammation, adaptation and pain. Unraveling the pathophysiological mechanisms by which leukocytes and its products interfere with myocyte function and adaptation, and muscle nociceptor neuron activation, will contribute to a better understanding of the immune system-skeletal muscle interface. We welcome the submission of Reviews, Original Research, Case Reports and Clinical Trial articles covering, but not restricted to, the following topics:

1. The pharmacological role of leukocytes and its products in the modulation of muscle nociceptor during exercise or muscle adaptation and damage; and in the mechanism of muscle loss, atrophy and myositis in inflammatory diseases that induce cachexia
2. Potential signaling pathways related to central processing of pain in muscle nociception that could be targeted pharmacologically.
3. Potential new therapeutics (anti-inflammatories, antioxidants, analgesics, polyphenols, immunobiologicals, cytokine/chemokine receptor antagonists) that target leukocytes and its products to control muscle pain induced by exercise, inflammatory muscle pain and non-inflammatory widespread muscle hyperalgesia.
4. Potential new therapeutics (polyphenols) targeting leukocytes and/its products that could be used alone or in association with physical training to promote analgesia in chronic painful inflammatory conditions.

Keywords: Leukocytes, inflammation, pain, exercise, skeletal muscle

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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