ArticleThe journal of headache and pain2025
Ex vivo stimulation of the trigeminal nucleus caudalis induces peripheral CGRP release in the trigeminal ganglion and reveals a distinct dopamine-endocannabinoid mechanism relevant to migraine.
Article in The journal of headache and pain, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- TRPV1‑mediated central sensitisation: Core mechanisms of migraine chronification and novel targeted therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- From bench to bedside: relevant animal models across the migraine attack phases.The journal of headache and pain · 2026Review
- Functional characterisation of dura mater αCGRP degradation fragments at vascular, immune, and CGRP receptor targets.The journal of headache and pain · 2026Article
- Review
- Overlapping pathways of migraine and the endocannabinoid system: Potential therapeutic targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- TRPM3 activation causes CGRP release in trigeminal neurons: Implications for migraine mechanisms.Headache · 2026Article
- Endocannabinoid Modulation in Headache: Mechanisms, Models, and Translational Therapies.Cells · 2026Review
- The microgenderome in migraine: integrating sex hormones, microbial composition, and metabolic profiles into a sex-related framework.Frontiers in microbiology · 2026Review
- From trigeminal ganglion to cortex: ATG7 emerges as a key integrator of migraine pathways via multi-omics profiling.The journal of headache and pain · 2025Article
- Endogenous treatments for migraine pain.The journal of headache and pain · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
backgroundCalcitonin gene-related peptide (CGRP) release from trigeminal structures is central to migraine pathophysiology. This study employed an ex vivo model preserving anatomical continuity between the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG) to investigate (1) whether TNC stimulation induces peripheral CGRP release from the TG and (2) the potential involvement of a distinct dopamine-endocannabinoid mechanism.
methodsTissues were dissected as a single unit and placed in custom 3D-printed chambers, allowing targeted stimulation of either the TNC or the TG while measuring CGRP in both compartments. Pharmacological tools, including capsaicin (TRPV1 agonist), KCl (depolarizing agent), dopamine, and selective enzyme inhibitors or receptor antagonists, were used to elucidate underlying signalling pathways. CGRP levels were quantified via enzyme-linked immunosorbent assay.
resultsStimulation of the TNC elicited a significant rise in CGRP release locally and in the TG compartment, whereas directly stimulating the TG did not trigger CGRP release in the TNC. Subsequent experiments showed that applying dopamine to the TNC further enhanced CGRP release. TRPV1 blockade or pharmacological inhibition of N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), an enzyme important for anandamide biosynthesis, markedly attenuated dopamine-induced CGRP release, indicating that an endocannabinoid-driven mechanism is involved.
conclusionActivating the TNC alone was sufficient to evoke CGRP release in the peripheral trigeminal compartment, underscoring a potential central-to-peripheral mechanism that may be relevant to migraine. Moreover, a dopamine-endocannabinoid-TRPV1 axis appears to modulate CGRP signalling in this system, indicating additional complexity and providing potential new strategies for migraine therapy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.