title: Different pathophysiology underlying animal models of fibromyalgia and neuropathic pain: comparison of reserpine-induced myalgia and chronic constriction injury rats.
abstract: The reserpine-induced myalgia (RIM) rat manifests fibromyalgia-like chronic pain symptoms. The present study explored the pathophysiology underlying the pain symptoms in the RIM rat and the chronic constriction injury (CCI) rat, an animal model of neuropathic pain as a reference. Nerve tissue samples were collected from the nociception-tested animals for pathological examinations. Additionally, the therapeutic efficacy of a sodium channel blocker mexiletine was assessed in both rats. A slight vacuolization in the substantia nigra (SN) occurred in some of the RIM rats without any other histopathological changes in the brain or peripheral neurons. All the RIM rats, with or without vacuolization, showed hypersensitivity to tactile, muscle pressure, and cold stimuli. In the CCI rat, neurodegenerative changes were apparent in the sciatic nerve and the spinal cord only. CCI rats displayed muscle hyperalgesia in addition to tactile and cold allodynia. Pharmacotherapy with mexiletine did not attenuate the pain in the RIM rat, although it was effective in the CCI rat. Taken together, it is not likely that pain symptoms in RIM rats are caused by degenerative changes at the level of primary afferents and spinal cord, as is the case for CCI rats. The significance of the vacuolization in the SN is less clear at present because of the minor extent of the change and the lack of correlation with nociceptive sensitivity. The pain symptoms in RIM rats could be associated with dysfunction of biogenic amines-mediated CNS pain control even without apparent pathologies in the nervous system.
authors.affiliation: Department of Pain Research, Pharmacology Research Labs, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. yukinori.nagakura@jp.astellas.com
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Nagakura
authors.forename: Masayasu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Takahisa
authors.initials: T
authors.lastname: Noto
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Sekizawa
authors.forename: Tomoya
authors.initials: T
authors.lastname: Oe
authors.forename: Eiji
authors.initials: E
authors.lastname: Yoshimi
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tamaki
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D059350:Chronic Pain; D003250:Constriction; D004195:Disease Models, Animal; D005356:Fibromyalgia / Q000139:chemically induced* / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D009437:Neuralgia / Q000209:etiology* / Q000503:physiopathology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology*; D012584:Sciatic Nerve / Q000293:injuries* / Q000503:physiopathology
chemical_list: D012110:Reserpine