Alleviation of mechanical allodynia by the inhibition of microglial interleukin-18 in the spinal cord

Microglia have been proposed to play a pivotal role by releasing proinflammatory cytokines in the central sensitization of spinal pain pathway. In the present study, we investigated the potential role of interleukin-18 (IL-18), mainly released by microglia, in the tetanic stimulation of the sciatic nerve (TSS) induced mechanical allodynia of rats. TSS produced bilateral mechanical allodynia and the increased expression of the microglial marker Iba-1 and IL-18. Single application of the IL-18 inhibitor IL-18 binding protein (IL-18BP, 4.5 μg/30 μl) transiently but significantly inhibited TSS-induced mechanical allodynia on the ipsilateral side at lh, 3h and 5h following intrathecal injection on day 5 after TSS. Double staining showed that IL-18 was colocalized predominantly with the microglial marker Iba-1 in the spinal superficial dorsal horn, slightly with the astrocytic marker GFAP, but not with the neuronal marker NeuN. The results suggest that spinal IL-18, mainly released from microglia, participates in the induction of TSS-induced central sensitization of pain pathway transmission.