title: Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model.
abstract: Chronic widespread pain is a serious medical problem, yet the mechanisms of nociception and pain are poorly understood. Using a reserpine-induced pain model originally reported as a putative animal model for fibromyalgia, this study was undertaken to examine the following: (1) expression of several ion channels responsible for pain, mechanotransduction, and generation/propagation of action potentials in the dorsal root ganglion (DRG), (2) activities of peripheral nociceptive afferents, and (3) alterations in spinal microglial cells. A significant increase in mRNA expression of the acid-sensing ion channel (ASIC)-3 was detected in the DRG, and the behavioral mechanical hyperalgesia was significantly reversed by subcutaneous injection of APETx2, a selective blocker of ASIC3. Single-fiber recordings in vitro revealed facilitated mechanical responses of mechanoresponsive C-fibers both in the skin and muscle although the proportion of mechanoresponsive C-nociceptors was paradoxically decreased. In the spinal dorsal horn, microglial cells labeled with Iba1 immunoreactivity was activated, especially in laminae I-II where the nociceptive input is mainly processed compared with the other laminae. The activated microglia and behavioral hyperalgesia were significantly tranquilized by intraperitoneal injection of minocycline. These results suggest that the increase in ASIC3 in the DRG facilitated mechanical response of the remaining C-nociceptors and that activated spinal microglia may direct to intensify pain in this model. Pain may be further amplified by reserpine-induced dysfunction of the descending pain inhibitory system and by the decrease in peripheral drive to this system resulting from a reduced proportion of mechanoresponsive C-nociceptors.
authors.affiliation: Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan Department of Physical Therapy, College of Life and Health Sciences, Chubu University, Kasugai, Japan Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Taguchi
authors.forename: Kimiaki
authors.initials: K
authors.lastname: Katanosaka
authors.forename: Masaya
authors.initials: M
authors.lastname: Yasui
authors.forename: Koei
authors.initials: K
authors.lastname: Hayashi
authors.forename: Mai
authors.initials: M
authors.lastname: Yamashita
authors.forename: Koji
authors.initials: K
authors.lastname: Wakatsuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yamanaka
authors.forename: Kazue
authors.initials: K
authors.lastname: Mizumura
mesh_terms: D062565:Acid Sensing Ion Channels / Q000235:genetics / Q000378:metabolism; D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation; D009412:Nerve Fibers / Q000502:physiology; D009431:Neural Conduction / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D010812:Physical Stimulation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000633:toxicity*; D012867:Skin / Q000294:innervation; D013116:Spinal Cord / Q000473:pathology
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D000959:Antihypertensive Agents; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D012110:Reserpine