Interaction of glia activation and neurotransmission in hippocampus of neuropathic rats treated with mirtazapine.

Recent studies have characterized a central nervous system neuroimmune effect in the analgesic mechanisms of antidepressants. Our study investigated the effect of a novel antidepressant mirtazapine on pro-inflammatory cytokines expression and astrocytic activation in hippocampus of neuropathic rats. L5 spinal nerve transection was made to produce mononeuropathic model. Mirtazapine was orally administered to rats that had been operated on daily for 14 days. Adrenergic or serotonergic receptor antagonist was intraperitoneally administered to examine their ability of blocking antinociceptive effect. In the region of hippocampus, TNFalpha and IL-1beta levels were assayed and the activity of astrocytes was immunostained with GFAP (glial fibrillary acidic protein) antibody. As a result, mirtazapine significantly inhibited the hyperalgesia produced by surgery, which was partially reversed by adrenergic and serotonergic antagonist. After surgery, the hippocampus demonstrated elevated TNFalpha and IL-1beta levels, concomitant with reactive astrocytes. Mirtazapine markedly reduced hippocampal cytokines production or astrocytic activation, which was blocked by both adrenergic and serotonergic antagonists. Our results indicate a possible role of hippocampal pro-inflammatory cytokines and glia in the pathogenesis of neuropathic pain. A potential analgesic mechanism of mirtazapine may be inhibiting the above neuroimmune action through affecting adrenergic and serotonergic system.