Search

The present study was performed to explore the modulatory potential of different endogenous opioid systems on transmission of presumed nociceptive information at the spinal cord level in thermally injured rats. Thermal injury was performed by dipping the left paw into water 60 degrees C for 20 s. This induced a significant bilateral decrease in hindpaw withdrawal latency HWL to pressure. Intrathecal administration of 10 nmol of CGRP8-37 induced a significant bilateral increase in HWL in the thermally injured group and in the intact controls. The effect of different opioid receptor antagonists on the increased latency to withdrawal response induced by intrathecal injection of 10 nmol of CGRP8-37 was explored in the thermally injured rats. The effect was reversed by intrathecal injection of 40 and 80 nmol of: b-funaltrexamine (mu opioid receptor antagonist) and naltrindole (delta opioid receptor antagonist), but not by norbinaltorphimine (kappa opioid receptor antagonist). The results of the present study show that intrathecal CGRP8-37 increases hindpaw withdrawal latency in thermally injured rats, an effect reduced by a mu as well as by a delta opioid receptor antagonist.

The Mu opioid receptor (MOR) has been shown to participate in the analgesic effect of the calcitonin gene-related peptide (CGRP) in the nucleus accumbens (NAc) of adult rats. However, it is not clear whether and how CGRP regulates the MOR at the molecular levels. In the present study, it is found that the level of MORs on the cell membrane of NAc neurons was increased twice more than the control level following CGRP treatment (1μM, 30min), which is a phenomenon that was blocked by the peptidergic antagonist CGRP8-37. No direct physical interaction was observed between MORs and CGRP receptors, and neither brefeldin A nor dynosore preincubation affected such effects of CGRP. However, addition of 20μM monensin 1h before CGRP treatment significantly blocked the action of CGRP on surface MORs. In living animals, microinjection of CGRP (1nmol in 1μl) into the NAc partially restored morphine antinociception in morphine-tolerant rats, and the effect of CGRP on surface MORs extended beyond normal NAc neurons to chronic morphine-treated NAc neurons. To conclude, these results demonstrate that CGRP can act on MORs and increase the number of surface MORs in NAc neurons, partially explaining the involvement of opioid receptors in CGRP-induced antinociception in the rat NAc.