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.