Infant Peripheral Nerve Injury Induces Delayed Neuropathic Pain And The Effect Of Exercise On The Neuropathic Pain

Background: Neuropathic pain is absent in infants and occurs years after injury.Adult spinal cord microglia play a key role in initiating neuropathic pain,but how is in infant remain to be explored.Modulation of microglia is a potential target for treating neuropathic pain,but whether it is effective in delayed neuropathic pain induced by infant nerve injury is still an enigma.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.Methods: Rat pups at postnatal day 3,10,21 and 33 received spared nerve injury,and behavior tests were performed to evaluate their pain threshold.q PCR,immunohistochemistry,and Western blot were used for M1 and M2 marker expression analysis.Exercise training was employed to counteract this delayed neuropathic pain behavior and microglia polarization,and potential mechanisms were also explored.Results: 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-? decreased after exercise,and intrathecal injection of the IL-10 antibody reduced the exercise-induced analgesia.Conclusions: 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.