title: Initial phase of neuropathic pain within a few hours after nerve injury in mice.
abstract: We tested a hypothesis that the spinal plasticity induced within a few hours after nerve injury may produce changes in cortical activities and an initial phase of neuropathic pain. Somatosensory cortical responses elicited by vibratory stimulation were visualized by transcranial flavoprotein fluorescence imaging in mice. These responses were reduced immediately after cutting the sensory nerves. However, the remaining cortical responses mediated by nearby nerves were potentiated within a few hours after nerve cutting. Nerve injury induces neuropathic pain. In the present study, mice exhibited tactile allodynia 1-2 weeks after nerve injury. Lesioning of the ipsilateral dorsal column, mediating tactile cortical responses, abolished somatic cortical responses to tactile stimuli. However, nontactile cortical responses appeared in response to the same tactile stimuli within a few hours after nerve injury, indicating that tactile allodynia was acutely initiated. We investigated the trigger mechanisms underlying the cortical changes. Endogenous glial cell line-derived neurotrophic factor (GDNF), found in the Meissner corpuscles, induced basal firing ∼0.1 Hz or less in its Aβ tactile afferents, and disruption of the basal firing triggered the potentiation of nontactile cortical responses. Application of 10 nm LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid], a specific antagonist of group II metabotropic glutamate receptors (mGluRs), on to the surface of the spinal cord also induced the potentiation of nontactile cortical responses. Together, it is suggested that low-frequency afferent firing produced by GDNF in touch-sensitive nerve fibers continuously activated spinal group II mGluRs and that failure of this activation triggered tactile allodynia.
authors: Department of Neurophysiology, Brain Research Institute, Niigata University, Chuo-ku, Niigata 951-8585, Japan.
authors: Seiji
authors: S
authors: Komagata
authors: Shanlin
authors: S
authors: Chen
authors: Akiko
authors: A
authors: Suzuki
authors: Haruyoshi
authors: H
authors: Yamashita
authors: Ryuichi
authors: R
authors: Hishida
authors: Takeyasu
authors: T
authors: Maeda
authors: Minoru
authors: M
authors: Shibata
authors: Katsuei
authors: K
authors: Shibuki
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods*; D010812:Physical Stimulation / Q000379:methods; D011984:Sensory Receptor Cells / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013997:Time Factors