title: Restraint stress impairs early wound healing in mice via alpha-adrenergic but not beta-adrenergic receptors.
abstract: Stress negatively influences wound healing in a clinically relevant manner. In an animal model, repeated restraint stress (RST) impairs wound healing in mice, partially through stress-induced glucocorticoid (GC) release. However, the role of stress-induced catecholamines (i.e., (nor)epinephrine) in healing has not been elucidated. In the present study, two 3.5mm round dermal wounds were placed on the backs of mice. Animals were restrained overnight for 3 days prior to and 5 days post-wounding. Prior to RST, mice were injected with either phentolamine or nadolol: non-specific alpha- and beta-adrenergic receptor antagonists, respectively. Pictures were taken daily to measure the rates of wound closure and contraction. Blockade of alpha-adrenergic, but not beta-adrenergic receptors, attenuated impairments in wound closure and contraction, and normalized edema, in RST mice. Thus, although stress impairment in wound healing clearly involves GCs, catecholamines play an important role via alpha-adrenergic receptor stimulation.
authors.affiliation: Laboratory for Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Eijkelkamp
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Engeland
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Gajendrareddy
authors.forename: Phillip T
authors.initials: PT
authors.lastname: Marucha
mesh_terms: D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009248:Nadolol / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012149:Restraint, Physical; D018709:Statistics, Nonparametric; D013315:Stress, Psychological / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000276:immunology*
chemical_list: D018674:Adrenergic Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D009248:Nadolol; D010646:Phentolamine