INTRATHECAL CGRP(8-37) RESULTS IN A BILATERAL INCREASE IN HINDPAW WITHDRAWAL LATENCY IN RATS WITH A UNILATERAL THERMAL-INJURY

The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide(8-37) (CGRP(8-37)) o n the hindpaw withdrawal latency (HWL) to pressure in rats with one th ermally injured hindpaw. Furthermore, the interaction of CGRP(8-37) an d naloxone was studied. Thermal injury was performed by dipping the le ft paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administratio n of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGR P(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 mu g respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like imm unoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P<0.001; right: P<0.05). There was also an incre ase in the amount of CGRP-like immunoreactivity in the cerebrospinal f luid (P<0.001), but not in plasma. The results indicate that CGRP play s a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.