title: The role of alpha-2 adrenoceptor subtype in the antiallodynic effect of intraplantar dexmedetomidine in a rat spinal nerve ligation model.
abstract: The purpose of this study was to examine the effects of intraplantar dexmedetomidine to relieve neuropathic pain and determine the role of peripheral α2-adrenoceptors. Neuropathic pain was induced by ligating the L5 and L6 spinal nerves in male Sprague-Dawley rats, and mechanical allodynia was assessed using von Frey filaments. Several antagonists were injected into the hindpaws to evaluate the mechanisms of action of dexmedetomidine, a nonselective α2-adrenoceptor antagonist yohimbine, an α2A-adrenoceptor antagonist BRL 44408, an α2B-adrenoceptor antagonist ARC 239, and a α2C-adrenoceptor antagonist JP 1302. The expression of α2A-adrenoceptor, α2B-adrenoceptor, and α2C-adrenoceptor genes in the lumbar segment of the spinal cord and the plantar skin of the nerve-injured leg was detected by reverse transcription-polymerase chain reaction. Ipsilateral intraplantar injection of dexmedetomidine produced dose-dependent antiallodynia. Ipsilateral, but not contraleral, intraplantar injection of yohimbine reversed the antinociception of dexmedetomidine. Intraplantar BRL 44408, ARC 239, and JP 1302 reversed the antinociception of dexmedetomidine. The expression levels of α2-adrenoceptor genes in the lumbar spinal cord did not differ between rats with neuropathic pain and naïve rats. The expression levels of α2B-adrenoceptor and α2C-adrenoceptor genes of plantar skin were upregulated significantly in the model group, whereas α2A-adrenoceptor expression was unchanged. These results suggest that intraplantar injection of dexmedetomidine produced an antiallodynic effect in spinal nerve ligation-induced neuropathic pain. All three types of peripheral α2A, α2B, and α2C-adrenoceptors were involved in the antiallodynic mechanism of dexmedetomidine.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, Gwangju, Republic of Korea.
authors.forename: Hyung Gon
authors.initials: HG
authors.lastname: Lee
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.forename: Yeo Ok
authors.initials: YO
authors.lastname: Kim
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D019771:Axotomy; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism*; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013127:Spinal Nerves / Q000378:metabolism / Q000601:surgery
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D018341:Receptors, Adrenergic, alpha-2; D020927:Dexmedetomidine
keywords: Adrenoceptors; Antiallodynia; Dexmedetomidine; Neuropathic pain; Peripheral