title: Activation of nicotinic acetylcholine receptors on bone marrow-derived cells relieves neuropathic pain accompanied by peripheral neuroinflammation.
abstract: 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. 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 α4 and α7 were up-regulated in the injured SCN. Increased α4 and α7 subunits were localized on both BM-derived macrophages and neutrophils. When nicotine (20nmol) was perineurally administered once a day for 4days (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 (20nmol), a non-selective antagonist for nAChRs. PSL-induced up-regulation of inflammatory cytokines and chemokines was suppressed by perineural administration of nicotine. Taken together, the expression of α4β2 and α7 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.
authors.affiliation: Department of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Kiguchi
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Takehiko
authors.initials: T
authors.lastname: Maeda
authors.forename: Shinta
authors.initials: S
authors.lastname: Tominaga
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Yohji
authors.initials: Y
authors.lastname: Fukazawa
authors.forename: Masanobu
authors.initials: M
authors.lastname: Ozaki
authors.forename: Shiroh
authors.initials: S
authors.lastname: Kishioka
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism*; D017931:DNA Primers; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009437:Neuralgia / Q000150:complications / Q000517:prevention & control*; D009538:Nicotine / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D011978:Receptors, Nicotinic; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009538:Nicotine