INTRATHECAL CGRP(8-37)-INDUCED BILATERAL INCREASE IN HINDPAW WITHDRAWAL LATENCY IN RATS WITH UNILATERAL INFLAMMATION

1 Recent work in our laboratory has demonstrated that intrathecal admi nistration of a selective antagonist of calcitonin gene-related peptid e (CGRP), CGRP(8-37), increased the hindpaw withdrawal latency (HWL) t o thermal stimulation and hindpaw withdrawal threshold (HWT) to pressu re in normal rats, and that these effects were more pronounced than in rats with mononeuropathy. 2 The present study was performed to invest igate the effects of intrathecal administration of CGRP(8-37) on the H WL and HWT in rats with unilateral hindpaw inflammation induced by sub cutaneous injection of carrageenin. The effect of naloxone was also st udied. 3 Subcutaneous injection of 0.1 ml of carrageenin into the plan tar region of the left hindpaw induced a significant increase in the v olume of the ipsilateral hindpaw (P< 0.001), and significant bilateral decreases of the HWL to thermal stimulation (ipsilateral: P<0.001; co ntralateral: P<0.01) and HWT to pressure (ipsilateral: P<0.001; contra lateral: P<0.01). 4 Intrathecal administration of 10 nmol of CGRP(8-37 ), but not of 1 or 5 nmol, induced a significant bilateral increase in the HWL and HWT in rats with experimentally induced inflammation (the rmal test: P<0.001; mechanical test: P<0.001). 5 The effect of intrath ecal administration of 10 nmol CGRPB(8-37) on HWL and HWT was signific antly more pronounced in intact rats than in rats with experimentally induced inflammation (ipsilateral: P<0.001; contralateral: P<0.001). 6 The effect of CGRP(8-37) on withdrawal responses in the inflamed paw was partly reversed by intrathecal injection of naloxone at a dose of 88 nmol in the thermal (ipsilateral: P<0.01; contralateral: P=0.14) an d mechanical tests (ipsilateral: P<0.05; contralateral: P=0.60). 7 A s ignificant bilateral increase in the concentration of CGRP-like immuno reactivity in the perfusate of both hindpaws was demonstrated 24 h aft er unilateral injection of carrageenin (ipsilateral: P<0.001; contrala teral: P<0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P<0.001), but not in plas ma (P=0.75). 8 The present study demonstrates that acute experimentall y-induced unilateral hindpaw inflammation, induces bilateral increases in the amount of CGRP-like immunoreactivity in hindpaw perfusates. In trathecal administration of CGRP(8-37) increased the HWL to thermal st imulation and HWT to pressure bilaterally. 9 The results indicate that CGRP plays a role in the transmission of presumed nociceptive informa tion in the spinal cord of rats with experimentally induced inflammati on. Furthermore, our findings suggest that opioids can modulate CGRP-r elated effects in the spinal cord.