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

Rasheen Powell, Violet A. Young, Kerri D. Pryce, Garrett D. Sheehan, Kwaku Bonsu, Abdulelah Ahmed and Arin Bhattacharjee ()
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Rasheen Powell: University at Buffalo - The State University of New York
Violet A. Young: University at Buffalo - The State University of New York
Kerri D. Pryce: University at Buffalo - The State University of New York
Garrett D. Sheehan: University at Buffalo - The State University of New York
Kwaku Bonsu: University at Buffalo - The State University of New York
Abdulelah Ahmed: University at Buffalo - The State University of New York
Arin Bhattacharjee: University at Buffalo - The State University of New York

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26100-6

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DOI: 10.1038/s41467-021-26100-6

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