title: Infant nerve injury induces delayed microglial polarization to the M1 phenotype, and exercise reduces delayed neuropathic pain by modulating microglial activity.
abstract: Neuropathic pain is absent in infants and emergent years after injury. Adult spinal cord microglia play a key role in initiating neuropathic pain, and modulation of microglia is a potential target for treating neuropathic pain. In this study, we evaluated the role of microglia after infant peripheral nerve injury and the effect of exercise on the delayed-onset neuropathic pain. Rat pups received spared nerve injury, and behavior tests were performed to evaluate their pain threshold. qPCR, immunohistochemistry, and Western blot were used for M1 and M2 marker expression analysis. In contrast to the microglial polarization to the M1 phenotype observed in the adult spinal cord, in infant nerve injury, microglial polarization immediately shifted to the M2 phenotype. In adolescence, microglia polarized to the M1 phenotype, which was concomitant with the emergence of neuropathic pain. Exercise shifted spinal cord microglia polarization to the M2 phenotype and reduced neuropathic pain. In addition, IL-10 increased and TNF-α decreased after exercise, and intrathecal injection of the IL-10 antibody reduced the exercise-induced analgesia. Our study found that infant nerve injury induced delayed spinal cord microglia polarization to the M1 phenotype and that exercise was effective in the treatment of delayed adolescent neuropathic pain via the modulation of microglial polarization.
authors.affiliation: Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Anesthesiology, Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Shiyan, Hubei, China.
authors.forename: Xingrui
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Laboratory, Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Shiyan, Hubei, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zmzscmc@sina.com.
authors.forename: Mazhong
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006930:Hyperalgesia / Q000378:metabolism; D017628:Microglia / Q000502:physiology*; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold; D059348:Peripheral Nerve Injuries / Q000378:metabolism; D010641:Phenotype; D010805:Physical Conditioning, Animal; D017208:Rats, Wistar; D013127:Spinal Nerves / Q000293:injuries* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Exercise; Infant; Microglia; Neuropathic pain