Inhibiting endocytosis in CGRP + nociceptors attenuates inflammatory pain-like behavior.

Autor: Powell R; Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Young VA; Program for Neuroscience, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Pryce KD; Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Sheehan GD; Program for Neuroscience, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Bonsu K; Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Ahmed A; Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA., Bhattacharjee A; Pharmacology and Toxicology, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA. ab68@buffalo.edu.; Program for Neuroscience, University at Buffalo - The State University of New York, Buffalo, NY, 14203, USA. ab68@buffalo.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Oct 04; Vol. 12 (1), pp. 5812. Date of Electronic Publication: 2021 Oct 04.
DOI: 10.1038/s41467-021-26100-6
Abstrakt: The advantage of locally applied anesthetics is that they are not associated with the many adverse effects, including addiction liability, of systemically administered analgesics. This therapeutic approach has two inherent pitfalls: specificity and a short duration of action. Here, we identified nociceptor endocytosis as a promising target for local, specific, and long-lasting treatment of inflammatory pain. We observed preferential expression of AP2α2, an α-subunit isoform of the AP2 complex, within CGRP + /IB4 - nociceptors in rodents and in CGRP + dorsal root ganglion neurons from a human donor. We utilized genetic and pharmacological approaches to inhibit nociceptor endocytosis demonstrating its role in the development and maintenance of acute and chronic inflammatory pain. One-time injection of an AP2 inhibitor peptide significantly reduced acute and chronic pain-like behaviors and provided prolonged analgesia. We evidenced sexually dimorphic recovery responses to this pharmacological approach highlighting the importance of sex differences in pain development and response to analgesics.
(© 2021. The Author(s).)
Databáze: MEDLINE
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