title: Adrenergic β2-receptor mediates itch hypersensitivity following heterotypic chronic stress in rats.
abstract: Chronic stress is widely considered to trigger or enhance itch, especially for pruritic dermatitis. However, the molecular mechanisms linking chronic stress and itch are still unknown. The present study aimed to elucidate the role of adrenergic signaling in itch hypersensitivity following heterotypic chronic intermittent stress (HIS) in rats. HIS significantly increased hindlimb scratching, but not forepaw swiping, induced by intradermal injection of 5-hydroxytryptamine (5-HT) in the rat cheek. Coadministration of stress mediators such as norepinephrine or epinephrine dose-dependently increased both 5-HT-induced hindlimb scratching and 5-HT-induced forepaw swiping. HIS-induced itch hypersensitivity was attenuated by blockade of sympathetic signaling through guanethidine treatment, and systemic administration of the β-adrenoceptor antagonist propranolol and the β2-adrenoceptor antagonist butoxamine, but not on treatment with an α-adrenoceptor antagonist phentolamine and a β1-adrenoceptor antagonist atenolol. Moreover, HIS selectively increased the expression of β2-adrenoceptors and proinflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nerve growth factor (NGF)] in rat skin. The β-blockers propranolol and butoxamine abolished the upregulation of proinflammatory factors. The β2-adrenoceptor agonist terbutaline was sufficient to enhance the skin expression of TNF-α and IL-1β and to increase 5-HT-induced scratching in naive rats. Pretreatment with TNF-α could increase 5-HT-induced scratching. Together, these results demonstrate that β2-adrenoceptors mediate itch hypersensitivity following chronic stress by inducing proinflammatory factors, such as TNF-α, in the skin.
authors.affiliation: aJiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University bInstitute of Neuroscience cJiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, School of Public Health, Soochow University, Suzhou, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Peng
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.forename: Xue-Long
authors.initials: XL
authors.lastname: Wang
authors.forename: Lei-Fang
authors.initials: LF
authors.lastname: Cao
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Luo
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D058672:Adrenergic beta-2 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002078:Butoxamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011537:Pruritus / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012867:Skin / Q000378:metabolism; D013315:Stress, Psychological / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; D002078:Butoxamine; D012701:Serotonin; D020932:Nerve Growth Factor; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine