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.

Abstract

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: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
Analgesia and Pain Management01:25

Analgesia and Pain Management

Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
Nociception01:44

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain. Thus, pain helps the...
Pain01:20

Pain

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...