(362) The effects of voluntary wheel running on pain

Abstract

Chronic pain is a major public health problem, afflicting more of the general population than cardiovascular disease, diabetes, and cancer combined. Despite the prevalence of chronic pain, clinically prescribed analgesics with high efficacy often have undesirable off-target effects. Exercise is commonly prescribed to chronic pain patients and gives rise to analgesia in some cases. Preclinical animal models support a conserved mechanism for exercise-induced analgesia as exercise attenuates hypersensitivity in rodent inflammatory and neuropathic pain models. The cellular mechanisms that mediate the therapeutic effects of exercise are not well characterized, though a role for neurotrophic factors has been suggested. Exercise significantly increases neurotrophic factor levels in the central nervous system, and in turn, is associated with enhanced functional plasticity. We hypothesize that analogous changes in the peripheral nervous system underlie exercise-induced analgesia. Understanding these mechanisms may aid development of novel analgesics. To investigate the behavioral effects of exercise in mice, we are testing the effects of voluntary wheel running on thermal and mechanical sensitivity and in acute pain models, as compared to sedentary control animals. To elucidate the cellular mechanisms underlying the effects of exercise, neurotrophic factor levels in dorsal root ganglia and spinal cord are being quantified biochemically as candidate signaling molecules involved in exercise-induced analgesia. These studies will enhance our understanding of both the molecular effects exercise, and more broadly, our comprehension of pain modulation. Supported by NINDS grant R01NS042595. Chronic pain is a major public health problem, afflicting more of the general population than cardiovascular disease, diabetes, and cancer combined. Despite the prevalence of chronic pain, clinically prescribed analgesics with high efficacy often have undesirable off-target effects. Exercise is commonly prescribed to chronic pain patients and gives rise to analgesia in some cases. Preclinical animal models support a conserved mechanism for exercise-induced analgesia as exercise attenuates hypersensitivity in rodent inflammatory and neuropathic pain models. The cellular mechanisms that mediate the therapeutic effects of exercise are not well characterized, though a role for neurotrophic factors has been suggested. Exercise significantly increases neurotrophic factor levels in the central nervous system, and in turn, is associated with enhanced functional plasticity. We hypothesize that analogous changes in the peripheral nervous system underlie exercise-induced analgesia. Understanding these mechanisms may aid development of novel analgesics. To investigate the behavioral effects of exercise in mice, we are testing the effects of voluntary wheel running on thermal and mechanical sensitivity and in acute pain models, as compared to sedentary control animals. To elucidate the cellular mechanisms underlying the effects of exercise, neurotrophic factor levels in dorsal root ganglia and spinal cord are being quantified biochemically as candidate signaling molecules involved in exercise-induced analgesia. These studies will enhance our understanding of both the molecular effects exercise, and more broadly, our comprehension of pain modulation. Supported by NINDS grant R01NS042595.