title: N-type voltage-dependent Ca2+ channel in non-excitable microglial cells in mice is involved in the pathophysiology of neuropathic pain.
abstract: Peripheral nerve injury induces neuropathic pain which is characterized by tactile allodynia and thermal hyperalgesia. N-type voltage-dependent Ca(2+) channel (VDCC) plays pivotal roles in the development of neuropathic pain, since mice lacking Cav2.2, the pore-forming subunit of N-type VDCC, show greatly reduced symptoms of both tactile allodynia and thermal hyperalgesia. Our study on gene expression profiles of the Cav2.2 knockout (KO) spinal cord after spinal nerve ligation (SNL)-injury revealed altered expression of genes known to be expressed in microglia, raising an odd idea that N-type VDCC may function in not only excitable (neurons) but also non-excitable (microglia) cells in neuropathic pain state. In the present study, we have tested this idea by using a transgenic mouse line, in which suppression of Cav2.2 expression can be achieved specifically in microglia/macrophage by the application of tamoxifen. We found SNL-operated transgenic mice exhibited greatly reduced signs of tactile allodynia, whereas the degree of thermal hyperalgesia was almost the same as that of control. Immunohistochemical analysis of the transgenic lumbar spinal cord revealed reduced accumulation of Iba1-positive cells (microglia/macrophage) around the injured neurons, indicating microglial N-type VDCC is important for accumulation of microglia at the lesion sites. Although the mechanism of its activation is not clear at present, activation of N-type VDCC expressed in non-excitable microglial cells contributes to the pathophysiology of neuropathic pain.
authors.affiliation: Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address: h-saegusa.mphm@tmd.ac.jp.
authors.forename: Hironao
authors.initials: H
authors.lastname: Saegusa
authors.affiliation: Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. Electronic address: t-tanabe.mphm@tmd.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tanabe
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D005260:Female; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology*; D009437:Neuralgia / Q000473:pathology* / Q000503:physiopathology*; D010147:Pain Measurement; D013127:Spinal Nerves / Q000473:pathology* / Q000503:physiopathology*
chemical_list: C500963:Cacna1b protein, mouse; D020864:Calcium Channels, N-Type
keywords: Ca(v)2.2; Conditional knockdown; Microglia; N-type voltage-dependent Ca(2+) channel; Neuropathic pain