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 1h, 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.