Modulation of glia activation in neuropathic pain
There is a growing body of evidence indicating that glial cells have causal role in the pathogenesis of pain hypersensitivity following nerve injury. We aimed to examine how chronic constriction injury (CCI) to the sciatic nerve infl uences glia activity markers, cytokine levels and expression of mGlu receptors in the spinal cord and dorsal root ganglia (DRG) as well as features of the neuropathic pain, such as allodynia and hyperalgesia in rats and mice. Our study showed that glial markers (C1q, GFAP), interleukins (IL-1β, IL-6) and mGlu receptor (mGlu5, mGlu3) mRNAs were strongly elevated ipsilaterally in the spinal cord after CCI. Microglial cells were more activated in the spinal cord in contrast to DRG where astrocytic activation prevailed. In the ipsilateral DRG, IL-1α, IL-6, and IL-10 mRNA levels were increased. Western blot analysis showed the presence of IL-1α protein in the DRG and down-regulation of these proteins after CCI. Minocycline and/or pentoxifylline administration reversed the injury-induced changes in glia markers and mGlu receptor mRNAs and protein levels, and signifi cantly attenuated CCI-induced allodynia and hyperalgesia. The implication of glial activation paralleled with upregulation of mGlu receptors in neurodegenerative processes suggests that pharmacological targeting of spinal microglia in chronic pain may provide an effective therapy for controlling clinical pain syndromes. Support: statutory funds of the Institute of Pharmacology, PAS.