Sex differences in the effects of calcitonin gene-related peptide signaling on migraine-like behavior in animal models: a narrative review.

Migraine is a common neurological disorder with a typical onset in adolescence or early adulthood. Migraine is three times more common in women than men, but the definitive cause underlying the observed disparity is not fully understood. Calcitonin gene-related peptide (CGRP) is a neuropeptide and potent vasodilator that is now clearly linked to migraine based on the efficacy of drugs targeting its signaling.

The role of amygdala calcitonin gene-related peptide receptors on the development of persistent bladder pain in mice.

Bladder pain significantly impacts millions worldwide, severely affecting their quality of life and posing a major clinical challenge. Understanding the mechanisms underlying persistent bladder pain is critical for developing better therapeutic strategies. In this study, we investigate the effects of cyclophosphamide (CYP)-induced persistent bladder sensitization to explore the lateralized contribution of amygdala calcitonin gene-related peptide receptors (CGRP-Rs) on pain-like changes in mice.

Antinociceptive Effects of 2/3-Subtype-Selective GABA Receptor Positive Allosteric Modulators KRM-II-81 and NS16085 in Male Rats: Behavioral Specificity.

Recent studies suggest that among the gamma-aminobutyric acid type A (GABA)receptor subtype heterogeneity, 2/3 subunits of GABA receptors mediate pain processing. Therefore, 2/3 subtype-selective GABA receptor-positive allosteric modulators (PAMs) may be candidate analgesics. Antinociceptive effects of 2/3 subtype-selective GABA receptor PAMs have been reported, but the behavioral effects of these compounds have not been systematically evaluated.

A Parabrachial-to-Amygdala Circuit That Determines Hemispheric Lateralization of Somatosensory Processing.

Background: The central amygdala (CeA) is a bilateral hub of pain and emotional processing with well-established functional lateralization. We reported that optogenetic manipulation of neural activity in the left and right CeA has opposing effects on bladder pain.

Methods: To determine the influence of calcitonin gene-related peptide (CGRP) signaling from the parabrachial nucleus on this diametrically opposed lateralization, we administered CGRP and evaluated the activity of CeA neurons in acute brain slices as well as the behavioral signs of bladder pain in the mouse.

Blockade of α1 subtype GABAA receptors attenuates the development of tolerance to the antinociceptive effects of midazolam in rats.

Benzodiazepines bind to and act on α1-3 and α5-containing GABAA receptors. Previous studies suggest that different GABAA receptor α-subtypes mediate the various behavioral effects of benzodiazepines, which raises the possibility of combining benzodiazepines with subtype-selective GABAA receptor antagonists to improve the therapeutic profiles of benzodiazepines. This study examined the GABAA receptor subtype mediation of the tolerance to midazolam-induced antinociception in rats.

Slow-sustained delivery of naloxone reduces typical naloxone-induced precipitated opioid withdrawal effects in male morphine-dependent mice.

Thousands of individuals die each year from opioid-related overdoses. While naloxone (Narcan®) is currently the most widely employed treatment to reverse opioid toxicity, high or repeated doses of this antidote often lead to precipitated opioid withdrawal (POW). We hypothesized that a slow linear release of naloxone from a nanoparticle would induce fewer POW symptoms compared to high-dose free naloxone.

Antinociceptive Effects of a Novel α2/α3-Subtype Selective GABA Receptor Positive Allosteric Modulator.

Pain remains a challenging clinical condition and spinal GABA receptors are crucial modulators of pain processing. α2/α3-subtype GABA receptors mediate the analgesic actions of benzodiazepines. Positive allosteric modulators (PAMs) at α2/α3-subtype GABA receptors may have analgesic potential.