Interaction between the spinal melanocortin and opioid systems in a rat model of neuropathic pain

Abstract

Background: The authors recently demonstrated that administration of the melanocortin-4 receptor antagonist SHU9119 decreased neuropathic pain symptoms in rats with a sciatic chronic constriction injury. The authors hypothesised that there is a balance between tonic pronociceptive effects of the spinal melanocortin system and tonic antinociceptive effects of the spinal opioid system. Therefore, they investigated a possible interaction between these two systems and tested whether opioid effectiveness could be increased through modulation of the spinal melanocortin system activity. Methods: In chronic constriction injury rats, melanocortin and opioid receptor ligands were administered through a lumbar spinal catheter, and their effects on mechanical allodynia were assessed by von Frey probing. Results: Naloxone (10-100 μg) dose-dependently increased allodynia (percent of maximum possible effect of -67 ± 9%), which is in agreement with a tonic antinociceptive effect of the opioid system. SHU9119 decreased allodynia (percent of maximum possible effect of 60 ± 13%), and this effect could be blocked by a low dose of naloxone (0.1 μg), which by itself had no effect on withdrawal thresholds. Morphine (1-10 μg) dose-dependently decreased allodynia (percent of maximum possible effect of 73 ± 14% with the highest dose tested). When 0.5 μg SHU9119 (percent of maximum possible effect of 47 ± 14%) was given 15 min before morphine, there was an additive antiallodynic effect of both compounds. Conclusions: Together, these data confirm that there is an interaction between the spinal melanocortin and opioid systems and that combined treatment with melanocortin-4 receptor antagonists and opioids might possibly contribute to the treatment of neuropathic pain.