Spinal Cord Stimulation Enhances Microglial Activation in the Spinal Cord of Nerve-Injured Rats

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(1 μg,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.