Original Article
Subject Category: Neurobiology
Journal of Investigative Dermatology (2007) 127, 1479–1488. doi:10.1038/sj.jid.5700661; published online 21 December 2006
Deletion of
- and
-Opioid Receptors in Mice Changes Epidermal Hypertrophy, Density of Peripheral Nerve Endings, and Itch Behavior
Mei Bigliardi-Qi1,2, Claire Gaveriaux-Ruff3, Katrin Pfaltz4, Pierre Bady5, Tommy Baumann1, Theo Rufli4, Brigitte L Kieffer3 and Paul L Bigliardi1,4
- 1Department of Dermatology, CHUV Hôpital Beaumont, Lausanne, Switzerland
- 2Department of Research, University of Basel, Basel, Switzerland
- 3Institute de Génétique et Biologie Moléculaire et Cellulaire IGBMC, CNRS/INSERM/ULP, Illkirch Cedex, France
- 4Department of Dermatology, University of Basel, Basel, Switzerland
- 5CEPIC, University of Lausanne, Lausanne, Switzerland
Correspondence: Dr Paul Bigliardi, Department of Dermatology, Neurodermatology, CHUV Hôpital de Beaumont, BT-440, CH-1011 Lausanne, Switzerland. E-mail: paul.bigliardi@chuv.ch
Received 10 May 2006; Revised 18 August 2006; Accepted 21 August 2006; Published online 21 December 2006.
Abstract
The
- (MOR) and
- (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 Th-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.
Abbreviations:
av, average value; KOR,
-opiate receptor; MOR,
-opiate receptor; PGP 9.5, protein gene product 9.5
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