title: Impaired diffuse noxious inhibitory controls in specific alternation of rhythm in temperature-stressed rats.
abstract: Fibromyalgia is characterized by chronic widespread musculoskeletal pain. A hypofunction in descending pain inhibitory systems is considered to be involved in the chronic pain of fibromyalgia. We examined functional changes in descending pain inhibitory systems in rats with specific alternation of rhythm in temperature (SART) stress, by measuring the strength of diffuse noxious inhibitory controls (DNIC). Hindpaw withdrawal thresholds to mechanical von Frey filament or fiber-specific electrical stimuli by the Neurometer system were used to measure the pain response. To induce DNIC, capsaicin was injected into the intraplantar of the forepaw. SART-stressed rats were established by exposure to repeated cold stress for 4 days. In the control rats, heterotopic intraplantar capsaicin injection increased withdrawal threshold, indicative of analgesia by DNIC. The strength of DNIC was reduced by naloxone (μ-opioid receptor antagonist, intraperitoneally and intracerebroventricularly), yohimbine (α2-adrenoceptor antagonist, intrathecally), and WAY-100635 (5-HT1A receptor antagonist, intrathecally) in the von Frey test. In SART-stressed rats, capsaicin injection did not increase withdrawal threshold in the von Frey test, indicating deficits in DNIC. In the Neurometer test, deficient DNIC in SART-stressed rats were observed only for Aδ- and C-fibers, but not Aβ-fibers stimulation. Analgesic effect of intracerebroventricular morphine was markedly reduced in SART-stressed rats compared with the control rats. Taken together, in SART-stressed rats, capsaicin-induced DNIC were deficient, and a hypofunction of opioid-mediated central pain modulation system may cause the DNIC deficit.
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka Higashi 2-chome Fujisawa, Kanagawa 251-8555, Japan. Electronic address: yasuo.itomi@takeda.com.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Itomi
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka Higashi 2-chome Fujisawa, Kanagawa 251-8555, Japan. Electronic address: yasuhiro.tsukimi@takeda.com.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsukimi
authors.affiliation: Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka Higashi 2-chome Fujisawa, Kanagawa 251-8555, Japan. Electronic address: toru.kawamura@takeda.com.
authors.forename: Toru
authors.initials: T
authors.lastname: Kawamura
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D059328:Diffuse Noxious Inhibitory Control / Q000187:drug effects; D018869:Heat-Shock Response / Q000187:drug effects; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009020:Morphine; D002211:Capsaicin
keywords: Capsaicin (PubChem CID: 1548943); Descending pain inhibitory systems; Diffuse noxious inhibitory controls; Duloxetine (PubChem CID: 60835); Fibromyalgia; Morphine (PubChem CID: 21118682); Naloxone (PubChem CID: 5464092); Naproxen (PubChem CID: 23681059); Pregabalin (PubChem CID: 5486971); Specific alteration of rhythm in temperature; WAY-100635 (PubChem CID: 5684); Yohimbine (PubChem CID: 6169)