title: The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia.
abstract: (±)-Tramadol hydrochloride (tramadol) is a widely used analgesic for the treatment of cancer pain and chronic pain. Although many animal studies have shown antinociceptive effects of tramadol in both acute and chronic pain, little is known about the effect of tramadol in putative animal models of fibromyalgia. In this study, we compared the antiallodynic effects of oral administration of tramadol in two kinds of rat chronic pain models, neuropathic pain induced by partial sciatic nerve ligation (PSL) and reserpine-induced myalgia (RIM). In PSL rats, the threshold for responses induced by tactile stimulation with von Frey filaments was significantly decreased seven days after the operation, suggesting that the operation induced tactile allodynia. Orally administered tramadol showed a potent and dose-dependent antiallodynic effect on PSL-induced allodynia. In RIM rats, the threshold was significantly decreased five days after reserpine treatment. Orally administered tramadol also attenuated reserpine-induced tactile allodynia. To explore the mechanism of the antiallodynic effect of tramadol in RIM rats, we investigated the effect of the opioid antagonist naloxone on the tramadol-induced analgesic effect in these rats. The effect of tramadol was partially antagonized by naloxone, suggesting that the opioid receptor is involved at least in part in the antiallodynic effect of tramadol in RIM rats. These data indicate that orally administered tramadol produced improvement in both PSL rats and RIM rats at similar doses and provide evidence that the opioid system is partly involved in the analgesic effect of tramadol in RIM rats.
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan. Electronic address: k.kaneko@po.nippon-shinyaku.co.jp.
authors.forename: Kumi
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Umehara
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Homan
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Oka
authors.affiliation: Research Laboratories, Nippon Shinyaku Co., Ltd., 14, Nishinosho-monguchi-cho, Kisshoin, Minami-ku, Kyoto 601-8550, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oyama
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy*; D004195:Disease Models, Animal; D005356:Fibromyalgia / Q000188:drug therapy*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol
keywords: Fibromyalgia; Naloxone; Neuropathic pain; Opioid; Partial sciatic nerve ligation; Reserpine; Tramadol