Abstract
It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.
Highlights
In clinic, inflammatory pain is one of the common chronic pain (Zhuo, 2008; Li S. et al, 2017; Tomic et al, 2018)
The results demonstrated that intra-anterior cingulate cortex (ACC) injection of calcitonin gene-related peptide (CGRP) induced antinociceptive effects in naïve rats, and blockade CGRP receptor by CGRP8-37 attenuated the CGRP-induced antinociception in ACC, indicating that the CGRP-induced antinociception may be mediated by CGRP receptor in ACC of naïve rats
The results demonstrated that blockade CGRP receptor by CGRP8-37 attenuated the CGRPinduced antinociception in ACC, indicating that the CGRPinduced antinociception may be mediated by CGRP receptor in ACC of rats with inflammatory pain
Summary
Inflammatory pain is one of the common chronic pain (Zhuo, 2008; Li S. et al, 2017; Tomic et al, 2018). It has been reported that ACC is involved in nociceptive modulation in acute and chronic inflammation (Bliss et al, 2016; Harris-Bozer and Peng, 2016; Zhang et al, 2017a). Zhang and her colleagues reported that galanin produced antinociceptive effect in ACC in inflammatory rats (Zhang et al, 2017a). The role of CGRP and CGRP receptor in pain regulation in the ACC in naïve rats and rats with inflammatory pain is worth exploring
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