Reversal of Neuropathic Pain with Exercise is Mediated by Endogenous Opioids
AuthorStagg, Nicola Jane
AdvisorMalan, Jr., T. Philip
Committee ChairMalan, Jr., T. Philip
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractExercise is often prescribed for patients with chronic pain, but there is little objective evidence supporting this recommendation. Therefore, we tested the effect of moderate aerobic exercise on the sensory hypersensitivity produced in an animal model of neuropathic pain. Male rats that underwent unilateral ligation of the L5 and L6 spinal nerves (SNL) were divided into exercise-trained or sedentary groups. Exercise training was performed using a treadmill, beginning 7 days after surgery, and continued 5 days a week for 5 weeks. Animals were exercised 30 min/day, at a speed of 14-16 m/min. Sensory testing was performed 23 hours after exercise training. Typical thermal and tactile hypersensitivity developed within 1 week after surgery. Treadmill training reversed thermal and tactile hypersensitivity in injured animals within 4 weeks, but had no effect on sham-operated or non-operated animals. One week after the cessation of exercise training, tactile hypersensitivity returned.The effects of exercise training on SNL-induced sensory hypersensitivity were reversed by the opioid receptor antagonist naloxone. Naloxone or naloxone methiodide reversed the effects of exercise when administered intracerebroventricularly (i.c.v.). Immunohistochemistry revealed increased immunostaining for B-endorphin and met-enkephalin in the periaquaductal grey (PAG) and rostral ventromedial medulla (RVM) regions of exercise-trained animals compared to sedentary animals. An ELISA immunoassay revealed a 31% increase in PAG B-endorphin content in exercise-trained SNL animals. More BDNF was also present in the brain's of exercise-trained animals compared to sedentary, specifically in the ventromedial hypothalamus, hippocampus, and outer rim of the PAG. Administering a BDNF sequestering agent reversed B-endorphin increases in the PAG of exercise-trained animals. Exercise-trained SNL animals treated with 25 ug BDNF sequestering agent (i.c.v.) had lower tactile thresholds compared to the exercise-trained vehicle group.These results support the recommendation of moderate aerobic exercise for patients suffering from neuropathic pain, and suggest that exercise-induced pain reversal results from the upregulation of endogenous opioids in the brainstem. Additionally, increased BDNF with exercise training may play a role in exercise-induced reversal of neuropathic pain by increasing the expression of endogenous opioids, but this needs to be verified further.
Degree ProgramPharmacology & Toxicology