Cutaneous Biology and Endogenous Opioids: How the Skin Modulates Pain and Addiction

Abstract

The Proopiomelanocortin gene, (POMC), produces many biologically active peptides including the endogenous opioid, β-endorphin, and the melanocortins: α-Melanocyte Stimulating Hormone, (αMSH), γMSH, βMSH and Adrenocorticotropic Hormone, (ACTH). βendorphin is released by the brain in response to stress or injury and is a potent analgesic. Melanocortins are well known for regulating pigmentation, metabolism, and cortisol levels. Additionally, opioids and melanocortins are known to have opposing actions in several settings including the regulation of pain and metabolism. The Melanocyte Stimulating Hormones are expressed in the skin where they bind the Melanocortin 1 Receptor on melanocytes and promote pigmentation. It has been reported that β-endorphin is also produced in the skin, however it was not believed to have a central effect. In this thesis I show that expression of these peptides in the skin is reflected in blood levels and affects nociception and behavior.