Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rat...Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic nerve.Male rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 post-CCI.SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns.SCS also upregulated the mRNAs of Ml-like markers,but not M2-like markers.Inducible NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after SCS.Intrathecal minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical hypersensitivity.Pretreatment with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain inhibition.These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.展开更多
基金the Neurosurgery Pain Research Institute at the Johns Hopkins University and subsidized by the National Institutes of Health(Bethesda,Maryland,USA)(NS 110598)supported by an award from the China Scholarship Council for Chinese PhD candidates to study abroad。
文摘Microglia can modulate spinal nociceptive transmission.Yet,their role in spinal cord stimulation(SCS)-induced pain inhibition is unclear.Here,we examined how SCS affects microglial activation in the lumbar cord of rats with chronic constriction injury(CCI)of the sciatic nerve.Male rats received conventional SCS(50 Hz,80%motor threshold,180 min,2 sessions/day)or sham stimulation on days 18-20 post-CCI.SCS transiently attenuated the mechanical hypersensitivity in the ipsilateral hind paw and increased OX-42 immunoreactivity in the bilateral dorsal horns.SCS also upregulated the mRNAs of Ml-like markers,but not M2-like markers.Inducible NOS protein expression was increased,but brain-derived neurotrophic factor was decreased after SCS.Intrathecal minocycline(1μg-100μg),which inhibits microglial activation,dosedependently attenuated the mechanical hypersensitivity.Pretreatment with low-dose minocycline(1μg,30 min)prolonged the SCS-induced pain inhibition.These findings suggest that conventional SCS may paradoxically increase spinal M1-like microglial activity and thereby compromise its own ability to inhibit pain.
