title: Modulation of C-nociceptive Activities by Inputs from Myelinated Fibers.
abstract: To understand the mechanisms of neuropathic pain caused by demyelination, a rapid-onset, completed but reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by single injection of cobra venom into the sciatic nerve, was created. Microfilament recording revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. Neuropathic pain behaviors including inflammatory response appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evans blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.
authors.affiliation: Department of Neurosurgery, Xuan Wu Hospital affiliated to Capital Medical University, Beijing, 100053, China.|Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China.
authors.forename: Wan-Ru
authors.initials: WR
authors.lastname: Duan
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100005, China. xieyk1938@126.com.
authors.forename: Yi-Kuan
authors.initials: YK
authors.lastname: Xie
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000503:physiopathology*; D004546:Elapid Venoms / Q000633:toxicity; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D007249:Inflammation; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009431:Neural Conduction; D009437:Neuralgia / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D059225:Nociception / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D004546:Elapid Venoms; D005070:Evans Blue
keywords: A-fiber demyelination; Antidromic discharges of C-fiber; C-polymodal nociceptors; Dorsal root reflexes; Neurogenic inflammatory pain