title: Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings, and itch behavior.
abstract: The mu- (MOR) and kappa- (KOR) opioid receptors have been implicated in the regulation of homeostasis of non-neuronal cells, such as keratinocytes, and sensations like pain and chronic pruritus. Therefore, we have studied the phenotype of skin after deletion of MOR and KOR. In addition, we applied a dry skin model in these knockout mice and compared the different mice before and after induction of the dermatitis in terms of epidermal thickness, epidermal peripheral nerve ending distribution, dermal inflammatory infiltrate (mast cells, CD4 positive lymphocytes), and scratching behavior. MOR knockout mice reveal as phenotype a significantly thinner epidermis and a higher density of epidermal fiber staining by protein gene product 9.5 than the wild-type counterparts. Epidermal hypertrophy, induced by the dry skin dermatitis, was significantly less developed in MOR knockout than in wild-type mice. Neither mast cells nor CD4 T(h)-lymphocytes are involved in the changes of epidermal nerve endings and epidermal homeostasis. Finally, behavior experiments revealed that MOR and KOR knockout mice scratch less after induction of dry skin dermatitis than wild-type mice. These results indicate that MOR and KOR are important in skin homeostasis, epidermal nerve fiber regulation, and pathophysiology of itching.
authors.affiliation: Department of Dermatology, CHUV Hôpital Beaumont, Lausanne, Switzerland.
authors.forename: Mei
authors.initials: M
authors.lastname: Bigliardi-Qi
authors.forename: Claire
authors.initials: C
authors.lastname: Gaveriaux-Ruff
authors.forename: Katrin
authors.initials: K
authors.lastname: Pfaltz
authors.forename: Pierre
authors.initials: P
authors.lastname: Bady
authors.forename: Tommy
authors.initials: T
authors.lastname: Baumann
authors.forename: Theo
authors.initials: T
authors.lastname: Rufli
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: Paul L
authors.initials: PL
authors.lastname: Bigliardi
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes; D002908:Chronic Disease; D003872:Dermatitis / Q000473:pathology / Q000503:physiopathology; D020405:Dermis / Q000294:innervation / Q000473:pathology / Q000502:physiology; D004817:Epidermis / Q000294:innervation / Q000473:pathology* / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006984:Hypertrophy; D008297:Male; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009411:Nerve Endings / Q000473:pathology*; D011537:Pruritus / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D013373:Substance P / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013373:Substance P; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse