Acute visceral pain relief mediated by A3AR agonists in rats: involvement of N-type voltage-gated calcium channels.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
31
01
2020
accepted:
14
04
2020
pubmed:
8
5
2020
medline:
15
5
2021
entrez:
8
5
2020
Statut:
ppublish
Résumé
Pharmacological tools for chronic visceral pain management are still limited and inadequate. A3 adenosine receptor (A3AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca2+ channels (Cav2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A3AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A3AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Cav2.2 blocker PD173212, and the clinically used drug linaclotide. A3AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Cav2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A3AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A3AR agonists inhibited Cav2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca2+ current was PD173212-sensitive and prevented by MRS1523. A3AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain.
Identifiants
pubmed: 32379223
pii: 00006396-202009000-00023
doi: 10.1097/j.pain.0000000000001905
pmc: PMC8272921
mid: NIHMS1716021
doi:
Substances chimiques
Adenosine A3 Receptor Agonists
0
Calcium Channels, N-Type
0
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2179-2190Subventions
Organisme : Intramural NIH HHS
ID : Z01 DK031117
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK031117
Pays : United States
Informations de copyright
Copyright © 2020 International Association for the Study of Pain.
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