Neuropathic pain: a possible role for the melanocortin system?

In humans, damage to the nervous system can lead to a pain state referred t o as neuropathic pain. Here, we give a short overview of the clinical pictu re and classification of neuropathic pain and highlight some of the current ly known pathophysiological mechanisms involved, with special emphasis on n europeptide plasticity. In this context, we discuss a specific group of neu ropeptides, the melanocortins. These peptides have been demonstrated to pla y a role in nociception and to functionally interact with the opiate system . Recently, we demonstrated that spinal melanocortin receptors are upregula ted in a rat model of neuropathic pain and that blockade of the melanocorti n MC4 receptor has anti-allodynic effects in this condition, suggesting tha t the melanocortin system plays a role in neuropathic pain. A natural agoni st of melanocortin receptors is alpha -melanocyte-stimulating hormone (alph a -MSH), derived from the precursor molecule pro-opiomelanocortin (POMC). C leavage of this precursor also yields beta -endorphin, which is co-released with alpha -MSH in nociception-associated areas of the spinal cord. We hyp othesise that melanocortin receptor blockade attenuates a tonic influence o f alpha -MSH on nociception, thus allowing the analgesic effects of beta -e ndorphin to develop, resulting in the alleviation of allodynia. In this way , treatment with melanocortin receptor antagonists might enhance opioid eff icacy in neuropathic pain, which would be of great benefit in clinical prac tice. (C) 2001 Published by Elsevier Science B.V.