Cellular mechanisms of neuroinflammatory pain: the role of interleukin-1beta.

Dorsal horn of the spinal cord is important in the transduction and modulation of various pain signals. Interleukin-1beta (IL-1beta) not only plays an important role in the nociceptive modulation but also enhances the spinal cord nociceptive neuron wind-up. Intrathecal (i.t.) administration of IL-1beta activates p38 mitogen-activated protein kinase (MAPK), and leads to induction of inducible nitric oxide synthase (iNOS) and release of nitric oxide (NO), which sensitizes the spinal nociceptors and produces thermal hyperalgesia and allodynia. I.t. pretreatment of IL-1 receptor antagonist (IL-1ra), p38 MAPK inhibitor or iNOS inhibitor, inhibits the i.t. IL-1beta-induced NO levels and thermal hyperalgesia in rats, likely via either inhibiting the IL-1beta-mediated p38 MAPK activation and subsequent iNOS induction, or direct attenuation of the central iNOS activity, which therefore reduces the central sensitization of inflammatory pain. I.t. administration of IL-1beta in rats provides an attractive model for studying the mechanisms and development of the treatment strategy of neuroinflammatory pain.