Involvement of spinal microglia in the anti-hyperalgesic effects of gabapentin in rat model of monoarthritis

【摘要】：正This study investigated the effects of gabapentin on thermal hyperalgesia and spinal glial activation evoked by monoarthritis(MA).MA produced a robust glial activation of microglia and astrocytes in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia.Intraperitoneal(i.p.) gabapentin significantly suppressed spinal microglial activation and blocked the development of thermal hyperalgesia in MA rats.Immunofluorescence showed that voltage-gated calcium channels(VGCCs),a proposed action target of gabapentin,were wildly distributed in primary afferent fibers terminals and dorsal horn neurons.Fractalkine(CX3CL1), a potential trigger to activate microglia,colocalized with VGCCs in superficial spinal cord,whereas its receptor CX3CR1 was mainly expressed in spinal microglia.These data suggest that the reduction of spinal glial activation by gabapentin is likely to be due to an action on glia via diminishing the release of the"pain"neurotransmitters/ neuromodulators from primary afferent terminals and spinal nociceptive neurons.