ArticleBritish journal of pharmacology2025
Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.
Article in British journal of pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Acupuncture modulates migraine-related neural and neuroendocrine regulatory pathways.The journal of headache and pain · 2026Review
- Peptidomics profiling identifies endogenous peptides associated with meningeal afferent activation in a chronic migraine mouse model.The journal of headache and pain · 2026Article
- PN6047 Demonstrates Broad Preclinical Efficacy in Headache Models as a Novel Delta-Opioid Receptor Agonist.bioRxiv : the preprint server for biology · 2026Article
- Light-aversion and cephalic allodynia in an intravenous CGRP model of migraine-like behaviour in male and female rats.The journal of headache and pain · 2026Article
- The microgenderome in migraine: integrating sex hormones, microbial composition, and metabolic profiles into a sex-related framework.Frontiers in microbiology · 2026Review
- Amplifying and ameliorating light avoidance in mice with photoreceptor targeting and calcitonin gene-related peptide sensitization.Headache · 2026Article
- PACAP versus CGRP in migraine: From mouse models to clinical translation.Cephalalgia : an international journal of headache · 2025Review
- Delta opioid receptors: Overlooked outlier or the next big thing.Current opinion in pharmacology · 2025Review
- Enhancement of the endocannabinoid system through monoacylglycerol lipase inhibition relieves migraine-associated pain in mice.The journal of headache and pain · 2025Article
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Authors and funding
9 authors.
Funding
Abstract
background and purposePituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor. EXPERIMENTAL APPROACH: Cephalic allodynia to low doses of acute and chronic PACAP were tested. A triptan (sumatriptan) and a CGRP receptor antagonist (olcegepant) were tested in this model. The δ-receptor agonist SNC80 was tested in PACAP and CGRP-induced headache models. Expression of PACAP, PAC1, CRLR and δ-receptors was determined using in situ hybridisation. KEY
resultsLow doses of PACAP produced dose-dependent acute and chronic cephalic allodynia, blocked by sumatriptan but not by olcegepant. The PAC1 antagonist (M65) did not inhibit CGRP-induced allodynia. There was moderate co-expression of PAC1 and CRLR transcripts in migraine-related regions. SNC80 blocked PACAP- and CGRP-induced allodynia. There was low co-expression of PACAP and δ-receptors in brain regions measured. However, there was high co-expression of PAC1 and δ-receptors in somatosensory cortex, hippocampus and trigeminal nucleus caudalis. CONCLUSION AND IMPLICATIONS: We developed a translationally significant model of PACAP-induced headache, which was mechanistically distinct from CGRP. Activation of δ-receptors blocked PACAP- and CGRP-induced allodynia, and δ-receptors were highly co-expressed with the PACAP-ergic system. Future studies will examine the functional relationship between δ-receptors and PAC1.
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