title: The role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex on allodynia following spared nerve injury.
abstract: The present study examined the role of α₂ adrenoceptor in mediating noradrenaline action in the ventrolateral orbital cortex (VLO) on allodynia induced by spared nerve injury (SNI) in the rat. The mechanical paw withdrawal threshold (PWT) was measured using von-Frey filaments. Microinjection of noradrenaline (1, 2, 4 μg in 0.5 μl) into the VLO, contralateral to the site of nerve injury, reduced allodynia; PWT increased in a dose-dependent manner. Similar to noradrenaline, microinjection of selective α₂ adrenoceptor agonist clonidine into the same VLO site also reduced allodynia, and was blocked by selective α₂ adrenoceptor antagonist yohimbine. Furthermore, administration of γ-aminobutyric acid A (GABAA) receptor antagonist bicuculline or picrotoxin to the VLO significantly enhanced clonidine-induced inhibition of allodynia, while GABAA receptor agonist muscimol or THIP (2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride) attenuated clonidine-induced inhibition. These results suggest that noradrenaline acting in the VLO can potentially reduce allodynia induced by SNI, and this effect is mediated by α₂ adrenoceptor. Moreover, GABAergic disinhibition may participate in α₂ receptor mediating effects in neuropathic pain in the central nervous system.
authors.affiliation: Department of Physiology and Pathophysiology, Xi'an Jiaotong University College of Medicine, Yanta Road W. 76#, Xi'an, Shaanxi 710061, PR China; Department of Physiology, Xi'an Medical University, Xinwang Road 1#, Xi'an, Shaanxi 710021, PR China.
authors.forename: Juan-Xia
authors.initials: JX
authors.lastname: Zhu
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Xu
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Qu
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Tang
authors.forename: Devin M
authors.initials: DM
authors.lastname: Barry
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Du
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Huo
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000503:physiopathology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018756:GABA Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine; D001640:Bicuculline
keywords: (+)-bicuculline, (S), 9(R); 2,5,6,7-retrahydroisoxazolo(5,4-c)pyridine-3-ol hydrochloride; Allodynia; Bicuculline; Clonidine; GABA; GABAergic modulation; L-(−)-norepinephrine (+)-bitartrate salt monohydrate; Muscimol; Neuropathic pain; Noradrenaline; PAG; PWT; SNI; Sm; THIP; VLO; Ventrolateral orbital cortex; Yohimbine; clonidine hydrochloride; muscimol hydrochloride; nucleus submedius; paw withdrawal threshold; periaqueductal gray; spared nerve injury; ventrolateral orbital cortex; yohimbine hydrochloride; α(2) adrenoceptor; γ-aminobutyric acid