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Updated: May 20, 2026

Intracranial Pharmacotherapy and Pain Assays in Rodents
Published on: April 9, 2019
δ-Opioid receptor agonist SNC80 induces central antinociception mediated by Ca2+ -activated Cl- channels
Daniela da Fonseca Pacheco1, Cinthia Mara da Fonseca Pacheco, Igor Dimitri Gama Duarte
1Department of Pharmacology, Institute of Biological Sciences, Federal University of Minas Gerais School of Biological Sciences and Health, University Center Newton Paiva, Belo Horizonte, Brazil.
Objectives:
The aim of this study was to determine whether Ca(2+)-activated Cl(-) channels (CaCCs) are involved in central antinociception induced by the activation of µ-, δ- and κ-opioid receptors.
Methods:
The nociceptive threshold for thermal stimulation was measured using the tail-flick test in Swiss mice. The drugs were administered via the intracerebroventricular route. Probabilities values of P < 0.05 were considered to be statistically significant (analysis of variance/Bonferroni test).
Key Findings:
The results demonstrate that exposure to the CaCC blocker niflumic acid (2, 4 and 8 µg) partially reverses the central antinociception induced by the δ-opioid receptor agonist SNC80 ((+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide; 4 µg). In contrast, niflumic acid did not modify the antinociceptive effect of the µ-opioid receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (0.5 µg) or κ-opioid receptor agonist bremazocine (4 µg).
Conclusions:
These data provide evidence for the involvement of CaCCs in δ-opioid receptor-induced central antinociception resulting from receptor activation by the agonist SNC80. CaCC activation does not appear to be involved when µ- and κ-opioid receptors are activated.
Insights
Calcium-activated chloride channels (CaCCs) are involved in delta-opioid receptor-mediated pain relief. However, CaCCs do not appear to mediate antinociception via mu- or kappa-opioid receptors.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Opioid receptors (µ, δ, κ) are key targets for pain management.
- Central antinociception involves complex signaling pathways.
- Calcium-activated chloride channels (CaCCs) play roles in neuronal excitability.
Purpose of the Study:
- To investigate the role of CaCCs in central antinociception induced by µ-, δ-, and κ-opioid receptor activation.
- To determine if CaCC blockers affect opioid-mediated pain relief.
Main Methods:
- Tail-flick test in Swiss mice to measure nociceptive thresholds.
- Intracerebroventricular drug administration.
- Statistical analysis using ANOVA with Bonferroni correction.
Main Results:
- Niflumic acid, a CaCC blocker, partially reversed antinociception induced by the δ-opioid agonist SNC80.
- Niflumic acid did not affect antinociception from µ-opioid agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin or κ-opioid agonist bremazocine.
Conclusions:
- CaCCs are involved in δ-opioid receptor-mediated central antinociception.
- CaCC activation is not implicated in µ- or κ-opioid receptor-induced antinociception.
Related Concept Videos
Opioid Receptors: Overview
Analgesia and Pain Management
Opioid Analgesics: Morphine and Other Natural Cogeners
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Nociception
Pain
