Abstract
Calcitonin gene-related peptide (CGRP), acting through CGRP1 receptors, produced behavioral signs of hyperalgesia in rats and sensitization of wide dynamic range (WDR) neuron in the spinal cord dorsal horn (Sun, et al., 2003). Although, involvement of CGRP receptors in central sensitization has been confirmed, the second messenger systems activated by CGRP receptor stimulation and that are involved in pain transmission are not clear. This study tested whether the hyperalgesic and wide dynamic range (WDR) neuron sensitizing effects of CGRP receptor activation is medicated by PKA or PKC signaling. Intrathecal injection of CGRP in rats produced mechanical hyperalgesia, as shown by paw withdrawal threshold tests. CGRP-induced hyperalgesia was attenuated significantly by the CGRP1 receptor antagonist, CGRP8-37. The effect was attenuated significantly by a protein kinase A (PKA) inhibitor (H89) or a protein kinase C (PKC) inhibitor (chelerythrine chloride). Electrophysiological experiments demonstrated that superfusion of the spinal cord with CGRP induced the sensitization of spinal dorsal horn neurons. The effect could be blocked by CGRP8-37. Either a PKA or a PKC inhibitor (H89 or chelerythrine) also attenuated this effect of CGRP. These results are consistent with the hypothesis that CGRP produces hyperalgesia by a direct action on CGRP receptors in the spinal cord dorsal horn and that this effect of CGRP is dependent on PKA and PKC signaling. In conclusion, CGRP produces mechanical hyperalgesia and sensitizes WDR neurons in dorsal horn in the absence of nerve injury via an action at CGRP1 receptors. These effects of CGRP are mediated by both PKA and PKC second-messenger pathways. Supported by NIH grants NS09743 and NS11255.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call