神経因性疼痛発症に関与するミクログリア由来BDNF

抄録

Microglia play an important role as immune cells in the central nervous system. Recently, accumulating evidences indicate the important role of ATP receptors of activated microglia in the neuropathic pain. Neuropathic pain is often a consequence of nerve injury through surgery, bone compression, cancer, diabetes or infection. The expression of P2X4 receptor is enhanced in spinal microglia after peripheral nerve injury model, and blocking pharmacologically and suppressing molecularly P2X4 receptors produce a reduction of the neuropathic pain (Tsuda et al. Nature 424, 778-783, 2003). Several cytokines such as interleukin-6 and tumor necrosis factor in the dorsal horn are also increased after nerve lesion and have been implicated in contributing to nerve-injury pain. ATP can activate MAPK leading to the release of bioactive substances including cytokines from microglia (Shigemoto-Mogami et al., J Neurochem 78, 1339-1349, 2001; Suzuki et al., J Neurosci 24, 1-7, 2004). Thus, diffusible factors released from activated microglia by the stimulation of purinergic receptors may have an important role in the development of neuropathic pain (Tsuda, M., Inoue, K., & Salter, M.W. Trend Neurosci 28, 101-107, 2005). I will discuss the mechanism of P2X4-evoked allodynia with an effect of a neurotrophic factor from activated microglia based on the latest our findings (Nature, in press). [J Physiol Sci. 2006;56 Suppl:S49]