Chronic blockade of melanocortin receptors alleviates allodynia in rats with neuropathic pain

We investigated the involvement of the spinal cord melanocortin (MC) system in neuropathic pain. Because we recently demonstrated that MC receptor lig ands acutely alter nociception in an animal model of neuropathic pain, in t his study we tested whether chronic administration was also effective. We h ypothesized that chronic blockade of the spinal MC system might decrease se nsory abnormalities associated with this condition. The effects of the MC r eceptor antagonist SHU9119 (0.5 mug/d) and agonist MTII (0.1 mug/d) were ev aluated in rats with a chronic constriction injury of the sciatic nerve. Dr ugs were continuously infused into the cisterna magna. Antinociceptive effe cts were measured with tests involving temperature (10 degreesC or 47.5 deg reesC) or mechanical (von Frey) stimulation. The administration of MTII inc reased mechanical allodynia, whereas SHU9119 produced a profound cold and m echanical antiallodynia, altering responses to control levels. The antiallo dynic effects of SHU9119 were very similar to those produced by the alpha ( 2)-adrenergic agonist tizanidine (50 mug/d). The effects of SHU9119 and MTI I are most likely mediated through the MC4 receptor, because this is the on ly MC-receptor subtype present in the spinal cord. We conclude that the chr onic administration of MC4-receptor antagonists might provide a promising t ool in the treatment of neuropathic pain.