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• W2045147289 abstract "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 GSK3β 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/GSK3β signaling pathway, AM could play a significant role in long-lasting heat hypersensitivity and inflammatory heat hyperalgesia." @default.
• W2045147289 created "2016-06-24" @default.
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• W2045147289 date "2006-10-24" @default.
• W2045147289 modified "2023-10-12" @default.
• W2045147289 title "A role for adrenomedullin as a pain-related peptide in the rat" @default.
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• W2045147289 doi "https://doi.org/10.1073/pnas.0602488103" @default.
• W2045147289 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1635121" @default.
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