Evidence map›Paper›PMID 38798444›Full record

ArticleResearch square2024

GLP-1 and Its Derived Peptides Mediate Pain Relief Through Direct TRPV1 Inhibition Without Affecting Thermoregulation.

Chul-Kyu Park, Eun Jin Go, Hyunjung Jo, Sung-Min Hwang, Md Mahbubur Rahman, Jaeik Park, Ji Yeon Lee, Youn Yi Jo, YunJae Jung, Temugin Berta and 1 more

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Article in Research square, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Chul-Kyu ParkGachon University.ORCID 0000-0002-4152-3022
Eun Jin GoGachon University.
Hyunjung JoGachon University.
Sung-Min HwangGachon University.
Md Mahbubur RahmanGachon University.
Jaeik ParkGachon University.
Ji Yeon LeeGil Medical Center, Gachon University.
Youn Yi JoGil Medical Center, Gachon University.
YunJae JungGachon University.
Temugin BertaUniversity of Cincinnati Medical Center.
Yong Ho KimGachon University.

Funding

Targeting sensory ganglia and glial signaling for the treatment of acute and chronic painR01NS113243 · NINDS · UNIVERSITY OF CINCINNATI · PI BERTA, TEMUGIN · 2019 to 2019
$2.0M
NINDS NIH HHS R01 NS113243
6 · The paper itself

Abstract

Hormonal regulation during food ingestion and its association with pain prompted the investigation of the impact of glucagon-like peptide-1 (GLP-1) on the transient receptor potential vanilloid 1 (TRPV1). Both endogenous and synthetic GLP-1 and an antagonist of GLP-1, exendin 9-39, reduced heat sensitivity in naïve mice. GLP-1-derived peptides (liraglutide, exendin-4, and exendin 9-39) effectively inhibited capsaicin (CAP)-induced currents and calcium responses in cultured sensory neurons and TRPV1-expressing cell lines. Notably, the exendin 9-39 alleviated CAP-induced acute pain, as well as chronic pain induced by complete Freund's adjuvant (CFA) and spared nerve injury (SNI) in mice, without causing hyperthermia associated with other TRPV1 inhibitors. Electrophysiological analyses revealed that exendin 9-39 binds to the extracellular side of TRPV1, functioning as a noncompetitive inhibitor of CAP. Exendin 9-39 did not affect proton-induced TRPV1 activation, suggesting its selective antagonism. Among exendin 9-39 fragments, exendin 20-29 specifically binds to TRPV1, alleviating pain in both acute and chronic pain models without interfering with GLP-1R function. Our study revealed a novel role for GLP-1 and its derivatives in pain relief, proposing exendin 20-29 as a promising therapeutic candidate.

Identifiers

PMID38798444
PMCPMC11118710

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