Voluntary Wheel Running Prevents Formation of Membrane Attack Complexes and Myelin Degradation After Peripheral Nerve Injury

Authors

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

Publication Date

1-1-2024

Journal

Brain Behavior Immunology

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.

Keywords

Humans, Rats, Animals, Myelin Sheath, Complement Membrane Attack Complex, Motor Activity, Peripheral Nerve Injuries, Hyperalgesia, Neuralgia, Sciatic Neuropathy, Sciatic Nerve

DOI

10.1016/j.bbi.2023.10.027

PMID

37924957

PMCID

PMC10842182

PubMedCentral® Posted Date

1-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes