IJNN :: IJNN Volume 2 :: Volume 2 - Issue 1 - October 2005 :: Volume 2 - Issue 1 - Reviews :: Vol 2 - Iss 1 - Review - The involvement of melanocortin 4 (MC4) receptors in the central mechanisms of opioid antinociception


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IJNN :: IJNN Volume 2 :: Volume 2 - Issue 1 - October 2005 :: Volume 2 - Issue 1 - Reviews :: Vol 2 - Iss 1 - Review - The involvement of melanocortin 4 (MC4) receptors in the central mechanisms of opioid antinociception

Vol 2 - Iss 1 - Review - The involvement of melanocortin 4 (MC4) receptors in the central mechanisms of opioid antinociception #16236

The involvement of melanocortin 4 (MC4) receptors
in the central mechanisms of opioid antinociception

Katarzyna Starowicz, Ryszard Przewlocki, Barbara Przewlocka

Department of Molecular Neuropharmacology, Institute of Pharmacoloy,
Polish Academy of Sciences, Cracow, Poland

Received 30 May 2005; accepted 26 August 2005

Correspondence and requests for reprints should be addressed to:
Prof Barbara Przewlocka
12 Smetna str
Cracow, 31-343
Poland
Tel: + 48 12 66 23 398
Fax: +48 12 637 45 00
E-mail: przebar@if-pan.krakow.pl

Abstract
The analgesic function of opioids is modulated by a range of non-opioid systems. These systems may modulate antinociception induced by exogenously administered opioids, and may be involved in the development of opioid tolerance, dependence and opioid insensitivity in some pain states. Among neuropeptides, melanocortins, can be considered as endogenous peptides with putative anti-opioid function. Interestingly, melanocortins are the product of enzymatic cleaveage of proopiomelanocortin, the same precursor molecule from which opioid peptides, e.g. β-endorphin, originate. The melanocortin and opioid systems have opposite activities in many tests, and, therefore, have been considered to be functional antagonists. Of all five cloned melanocortin receptors, the MC4 receptor attracts particular attention in the aspect of its role in these interactions. Nociception, which is one of the main functions of opioids, and opioid tolerance are the fields of possible interactions between melanocortins and opioids which may provide cues to elucidate nature of this phenomenon. A deeper understanding of interactions between opioids and melanocortins in the central nervous system may lead to development of new treatment strategies of chronic pain, opioid tolerance and addiction.

Key words

Melanocortins, opioids, neuropathic pain, morphine tolerance, spinal cord, dorsal root ganglia (DRG)

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