Antiallodynic effects of microglial interleukin-1β inhibition in the spinal cord

Microglia play a pivotal role in synaptic plasticity of chronic pain. In this study, the potential role of interleukin 1beta (IL-1β), mainly released by microglia in early stage of nerve injury, in mechanical allodynia induced by tetanic stimulation of the sciatic nerve (TSS) was examined. Mechanical allodynia was observed on both ipsilateral and contralateral sides of TSS. Moreover, the expression of the microglial marker Iba-1 and the proinflammatory cytokine IL-1β were significantly increased. Intrathecal injection of the IL-1 receptor antagonist (IL-1ra, 3.5 μg/ml, 20 μl/rat) 30 min before TSS significantly inhibited bilateral mechanical allodynia on day 3, 5 and 7 after TSS. Immunohistochemistry showed that IL-1β was colocalized with the microglial marker OX-42 in the spinal superficial dorsal horn, but not with the astrocytic marker GFAP and the neuronal marker NeuN on day 4 following TSS. The results demonstrate that microglial IL-1β participates in the hypersensitivity of pain behaviors induced by TSS.