Role of calcitonin gene-related peptide in nociception resulting from hind paw incision in rats

IntroductionThe superficial laminae of the spinal cord are crucial sites for the transmission of incoming noxious information. Calcitonin gene-related peptide (CGRP) is released from the presynaptic nerve terminals in these laminae. One of the objectives was to evaluate the temporospatial pattern of expression of CGRP following paw incision in rats. Paw incision-induced nociception mimics postoperative pain in humans. The next objective was to administer a specific CGRP receptor antagonist directly into the intrathecal space and observe the antinociceptive effect, which was then compared to morphine.Material and methodsSprague Dawley rats were subjected to incision on the right hind paw. The related spinal cord segments (L4-5) were isolated at different time intervals after incision and immunostained for CGRP. A different set of rats were implanted with intrathecal catheter and administered saline (control) or BIBN 4096 (CGRP antagonist) or morphine (10 μg/10 μl) and then subjected to paw incision. Nociception was evaluated at different time intervals up to day 7.ResultsExpression of CGRP was observed over laminae I and outer part of lamina II. Synaptic terminals could be discerned containing CGRP. Following incision, the expression decreased abruptly at 2 h. However, at 12 h, the expression had increased. Between days 1-5, the expression decreased again towards basal levels. The antinociceptive effect of BIBN was comparatively less than morphine, which robustly inhibited all three pain parameters at 2 h after incision.DiscussionImmunohistochemistry revealed that CGRP was involved in the transmission of nociception. However, blocking its action did not produce a robust antinociceptive effect.