Background and purpose: Many studies demonstrated that calcitonin gene-related peptide (CGRP) plays nociceptive modulation in the brain. There are highly expressions of CGRP and CGRP receptors in theanterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study was performed to explore the role of CGRP in nociceptive modulation in anterior cingulate cortex in rats with neuropathic pain.
Methods: The neuropathic pain model was set up by chronic constriction injury (CCI) of the left sciatic nerve of rats. Hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulations were measured by Hot plate and Randall Selitto tests. CGRP and CGRP8- 37 were microinjected into ACC.
Results: We found that intra-ACC administration of CGRP induced significant antinociceptive effects in a dose-dependent manner in rats with neuropathic pain. Furthermore, the CGRP-induced antinociceptive effect was attenuated by intra-ACC injection of the CGRP receptor

antagonist CGRP8-37. Interestingly, the CGRP-induced antinociception was higher in rats with neuropathic pain than that in naïve rats. So we further detected the calcitonin receptor-like receptor (CLR, a main component of CGRP receptor) mRNA levels and CLR protein levels in ACC and found that there were significant increases in CLR mRNA levels and CLR protein concentration in ACC in rats with neuropathic

pain than that in naïve rats tested by RT-PCR and western blot.
Conclusion: The results showed that CGRP plays an important role in the transmission and/or modulation of nociceptive information in ACC in rats with neuropathic pain. There are up regulations in both CGRP receptor expression and CGRP-induced antinociception in rats with neuropathic pain.