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A role for adrenomedullin as a pain-related peptide in the rat.

Authors: Ma, W  Chabot, JG  Quirion, R 
Citation: Ma W, etal., Proc Natl Acad Sci U S A. 2006 Oct 24;103(43):16027-32. Epub 2006 Oct 16.
Pubmed: (View Article at PubMed) PMID:17043245
DOI: Full-text: DOI:10.1073/pnas.0602488103

Adrenomedullin (AM) belongs to the calcitonin gene-related peptide (CGRP) family and is a well known potent vasodilator. We show here that AM is a powerful pain-inducing neuropeptide. AM-like immunoreactivity is widely distributed in both CGRP-containing and lectin IB4-binding nociceptors in dorsal root ganglion and axon terminals in the superficial dorsal horn of the rat spinal cord. Specific binding sites for the radioligand, [(125)I]AM13-52 as well as immunoreactivity for receptor markers such as the calcitonin receptor-like receptor and three receptor-activity-modifying proteins are localized in the superficial dorsal horn, demonstrating the existence of AM/CGRP receptors in this region. Intrathecal injection of rat AM1-50, dose- and time-dependently, induced long-lasting heat hyperalgesia and increased the phosphorylation of Akt and GSK3beta in the dorsal horn. Pre- and posttreatments with the AM receptor antagonist AM22-52 and PI3 kinase inhibitors (LY294002 and Wortmannin) significantly blocked or reversed AM-induced heat hyperalgesia. Pre- and posttreatments with AM22-52 and Wortmannin also significantly blocked or reversed intraplantar capsaicin-induced heat hyperalgesia. Taken together, our results demonstrate that AM acts as a pain-inducing peptide in the dorsal horn. By activating specific receptors (likely AM2) and the PI3K/Akt/GSK3beta signaling pathway, AM could play a significant role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia.


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RGD Object Information
RGD ID: 1625316
Created: 2007-06-01
Species: All species
Last Modified: 2007-06-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.