The potentiating effect of calcitonin gene-related peptide on transient receptor potential vanilloid-1 activity and the electrophysiological responses of rat trigeminal neurons to nociceptive stimuli
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Growing evidence suggests that calcitonin gene-related peptide (CGRP) participates in trigeminal nociceptive responses. However, the role of CGRP in sensitization or desensitization of nociceptive transduction remains poorly understood. In this study, we sought to further investigate the CGRP-induced up-regulation of transient receptor potential vanilloid-1 (TRPV1) and the responses of trigeminal neurons to nociceptive stimuli. Rat trigeminal ganglion (TG) organ cultures and isolated trigeminal neurons were incubated with CGRP. An increase in TRPV1 levels was observed in CGRP-incubated TG organ cultures. CGRP potentiated capsaicin-induced increase in phosphorylated CaMKII levels in the TG organ cultures. The incubation of the trigeminal neurons with CGRP significantly increased the inward currents in response to capsaicin challenge, and this effect was inhibited by co-incubation with the CGRP receptor antagonist, BIBN4068BS or the inhibitor of protein kinase A, H-89. These findings reveal that CGRP acting on trigeminal neurons may play a significant role in facilitating cellular events that contribute to the peripheral sensitization of the TG in nociceptive transmission.
KeywordsTrigeminal ganglion CGRP TRPV1 Capsaicin Nociceptive transmission
This work was supported by grants from the Thailand Research Fund (TRF) to AS (Senior Scholar Fellowship), the TRF-Royal Golden Jubilee Ph.D. Program and the Office of the Higher Education Commission to DC and a TRF grant to the Institute of Molecular Biosciences (IRG5780009) and Mahidol University.
The individual contribution to the article of each author is declared following: (1) DC contributed to data acquisition and analysis and preparation of the drafting manuscript. (2) MC contributed to analysis and interpretation of data. (3) AS contributed to analysis and interpretation of data. (4) BC contributed to experimental design, analysis and interpretation of data and critically revised the manuscript.
Compliance with ethical standards
Conflict of interest
The authors have no financial or other relationship that could lead to a conflict of interest. None of the authors have any competing interests.
All of the experiments in this study were conducted in accordance with the NIH Guidelines for the Care and Use of Animals, and the protocols were approved by the Institute of Molecular Biosciences Animal Care and Use Committee (MB-ACUC) of Mahidol University, Thailand (COA. No. MB-ACUC 2011/002) and the Macquarie University Animal Ethics Committee (approval 2012/058).
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