Voluntary wheel running prevents formation of membrane attack complexes and myelin degradation after peripheral nerve injury

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Green-Fulgham, Suzanne M. ; Lacagnina, Michael J. ; Willcox, Kendal F. ; Li, Jiahe ; Harland, Michael E. ; Ciena, Adriano Polican ; Rocha, Igor R. Correia ; Ball, Jayson B. ; Dreher, Renee A. ; Zuberi, Younus A. ; Dragavon, Joseph M. ; Chacur, Marucia ; Maier, Steven F. ; Watkins, Linda R. ; Grace, Peter M.

• Document type: Journal article
• Source: BRAIN BEHAVIOR AND IMMUNITY; v. 115, p. 13-pg., 2023-11-09.

Abstract

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor CD59. The levels of upstream complement components (C3) and their inhibitors (CD55, CR1 and CFH) were altered by CCI, but not increased by voluntary wheel running. Since MAC can degrade myelin, which in turn contributes to neuropathic pain, we evaluated myelin integrity at the sciatic nerve injury site. We found that the loss of myelinated fibers and decreased myelin protein which occurs in sedentary rats following CCI was not observed in rats with prior running. Substitution of prior voluntary wheel running with exogenous CD59 also attenuated mechanical allodynia and reduced MAC deposition at the nerve injury site, pointing to CD59 as a critical effector of the neuroprotective and antinociceptive actions of prior voluntary wheel running. This study links attenuation of neuropathic pain by prior voluntary wheel running with inhibition of MAC and preservation of myelin integrity at the sciatic nerve injury site. (AU)

• FAPESP's process: 21/02897-4 - Effect of photobiomodulation treatment on mitochondrial dynamics: analysis of the dorsal root ganglion in a type 1 Diabetes mellitus model
• Grantee: Marucia Chacur
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/13470-9 - Chemogenetic tools to determine the neuroimmune basis of pathological pain
• Grantee: Marucia Chacur
• Support Opportunities: Scholarships abroad - Research