Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms

Abstract

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain

“…In general, studies will differentiate between aerobic and anaerobic exercises, and how each type of muscle contraction acts on pain. We suggest some review articles on this topic [40,41,[97][98][99][100]. [87,88].…”

“…In general, studies will differentiate between aerobic and anaerobic exercises, and how each type of muscle contraction acts on pain. We suggest some review articles on this topic [40,41,[97][98][99][100]. Current pharmacological approaches consist of the medical prescription of seven main classes of drugs: (1) serotonin-and noradrenaline modulating antidepressants, (2) sodiumblocking anticonvulsants, (3) calcium-modulating anticonvulsants, (4) tramadol, (5) opioids, (6) capsaicin, and (7) local anesthetics [79].…”

Interactions and Trends of Interleukins, PAI-1, CRP, and TNF-α in Inflammatory Responses during the Perioperative Period of Joint Arthroplasty: Implications for Pain Management—A Narrative Review

“…Similarly, dorsal horn neurons in the spinal cord express receptors for these immune mediators, including pro-inflammatory cytokines such as IL-1β [47][48][49][50][51], TNF-α [52][53][54][55][56][57][58], IL-6 [59,60], and IL-17. The activation of these cytokine receptors on neurons influences neuronal function.…”