The calcitonin gene-related peptide antagonist CGRP8-37 increases the latency to withdrawal responses bilaterally in rats with unilateral experimental mononeuropathy, an effect reversed by naloxone.

The present study was performed in rats with experimental mononeuropathy after left common sciatic nerve constriction. A bilateral decrease in hindpaw withdrawal latency to thermal and mechanical stimulation was observed after unilateral ligation of the left common sciatic nerve; however, it was more pronounced on the lesioned side. Compared with sham-operated rats, the content of calcitonin gene-related peptide-like immunoreactivity was significantly decreased in the left dorsal horn of the spinal cord and left dorsal root ganglia in rats with mononeuropathy. Blocking the receptor of calcitonin gene-related peptide, by intrathecal injection of 5 or 10 nmol of calcitonin gene-related peptide (8-37), induced a significant bilateral increase in hindpaw withdrawal latency to both thermal and mechanical stimulation which, however, was significantly less pronounced in mononeuropathic rats than in intact rats. The effect of calcitonin gene-related peptide (8-37) was reversed by intrathecal administration of the opioid antagonist naloxone. The contribution of calcitonin gene-related peptide and its receptors to transmission of presumed nociceptive information appears to be reduced in the sciatic nerve constriction model. The decrease in reflex responsiveness induced by calcitonin gene-related peptide (8-37) was counteracted by naloxone, indicating that opioids control the net effect of excitation in the spinal cord circuitry induced by calcitonin gene-related peptide and possibly other co-released neurotransmitters.