Activation of nicotinic acetylcholine receptors on bone marrow-derived cells relieves neuropathic pain accompanied by peripheral neuroinflammation

作者：Kiguchi Norikazu; Kobayashi Yuka; Maeda Takehiko; Tominaga Shinta; Nakamura Jun; Fukazawa Yohji; Ozaki Masanobu; Kishioka Shiroh^*

来源：Neurochemistry International, 2012, 61(7): 1212-1219.

DOI：10.1016/j.neuint.2012.09.001

• Nicotine
• Cytokine
• Chemokine
• Macrophage
• Neutrophil
• Sciatic nerve

Emerging evidence indicates that chronic neuroinflammation plays a pivotal role in neuropathic pain. We explored whether activation of the nicotinic acetylcholine receptor (nAChRs) pathway on peripheral immune cells improves neuropathic pain. Mice were subjected to partial sciatic nerve ligation (PSL). Enhanced green fluorescent protein (EGFP)-chimeric mice were generated by transplantation of EGFP(+) bone marrow (BM) cells from EGFP-transgenic mice into wild-type mice. %26lt;br%26gt;EGFP(+) BM-derived cells infiltrated the injured sciatic nerve (SCN) of EGFP-chimeric mice, and these cells were found to be F4/80(+) macrophages and Ly6G(+) neutrophils. The protein expression of nAChR subunit alpha 4 and alpha 7 were up-regulated in the injured SCN. Increased alpha 4 and alpha 7 subunits were localized on both BM-derived macrophages and neutrophils. When nicotine (20 nmol) was perineurally administered once a day for 4 days (days 0-3), PSL-induced tactile allodynia and thermal hyperalgesia were significantly prevented. Relieving effects of nicotine on neuropathic pain were reversed by co-administration of mecamylamine (20 nmol), a non-selective antagonist for nAChRs. PSL-induced up-regulation of inflammatory cytokines and chemokines was suppressed by perineural administration of nicotine. %26lt;br%26gt;Taken together, the expression of alpha 4 beta 2 and alpha 7 subtypes of nAChRs may be increased on circulating macrophages and neutrophils in injured peripheral nerves. Activation of nAChRs on immune cells may relieve neuropathic pain accompanied by the suppression of neuroinflammation.

• 出版日期2012-12