In humans, damage to the nervous system can lead to a
pain state referred to as
neuropathic pain. Here, we give a short overview of the clinical picture and classification of
neuropathic pain and highlight some of the currently known pathophysiological mechanisms involved, with special emphasis on
neuropeptide plasticity. In this context, we discuss a specific group of
neuropeptides, the
melanocortins. These
peptides have been demonstrated to play a role in nociception and to functionally interact with the
opiate system. Recently, we demonstrated that spinal
melanocortin receptors are upregulated in a rat model of
neuropathic pain and that blockade of the
melanocortin MC(4) receptor has anti-allodynic effects in this condition, suggesting that the
melanocortin system plays a role in
neuropathic pain. A natural agonist of
melanocortin receptors is
alpha-melanocyte-stimulating hormone (
alpha-MSH), derived from the precursor molecule
pro-opiomelanocortin (
POMC). Cleavage of this precursor also yields
beta-endorphin, which is co-released with
alpha-MSH in nociception-associated areas of the spinal cord. We hypothesise that
melanocortin receptor blockade attenuates a tonic influence of
alpha-MSH on nociception, thus allowing the
analgesic effects of
beta-endorphin to develop, resulting in the alleviation of
allodynia. In this way, treatment with
melanocortin receptor antagonists might enhance
opioid efficacy in
neuropathic pain, which would be of great benefit in clinical practice.