Acute visceral pain relief mediated by A3AR agonists in rats: involvement of N-type voltage-gated calcium channels.

摘要: ABSTRACT Pharmacological tools for chronic visceral pain management are still limited and inadequate. A3 adenosine receptor (A3AR) agonists effective in different models of persistent pain. Recently, their activity has been related to the block N-type voltage-gated Ca2+ channels (Cav2.2) dorsal root ganglia (DRG) neurons. The present work aimed evaluate efficacy A3AR reducing postinflammatory hypersensitivity both male female rats. Colitis was induced by intracolonic instillation 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg 0.25 mL 50% EtOH). Visceral assessed measuring visceromotor response abdominal withdrawal reflex colorectal distension. effects (MRS5980 Cl-IB-MECA) were evaluated over time after DNBS injection compared that selective Cav2.2 blocker PD173212, clinically used drug linaclotide. significantly reduced DNBS-evoked (14 21 days injection) persistence (28 35 DNBS) phases. Efficacy comparable PD173212 fully control values, highlighting role Cav2.2. MRS5980 Cl-IB-MECA completely abolished antagonist MRS1523. Furthermore, patch-clamp recordings showed inhibited neurons isolated from either or DNBS-treated effect on current PD173212-sensitive prevented relieving DNBS, suggesting a potential therapeutic against