ArticleMolecular pain
Neurokinins and their receptors in the rat trigeminal system: Differential localization and release with implications for migraine pain.
Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Rimegepant for vestibular and cochlear symptoms associated with vertigo in a real-world retrospective study.iScience · 2026Article
- A delayed endothelial-glial mechanism for CGRP-induced migraine.The journal of headache and pain · 2026Review
- CGRP-targeted migraine treatment and early pathophysiology in experimental subarachnoid hemorrhage.The journal of headache and pain · 2026Article
- TRPM3 activation causes CGRP release in trigeminal neurons: Implications for migraine mechanisms.Headache · 2026Article
- Meningeal neuropeptide and neuroimmune interactions in the context of migraine.The journal of headache and pain · 2026Review
- Nutrition and Physical Activity in an Interdisciplinary Approach to Migraine: A Narrative Review.Nutrients · 2025Review
- Exploring the Link Between Inflammatory Biomarkers (SII, SIRI, PLR, NLR, LMR) and Migraine in Young and Early Middle-Aged US Adults: Evidence From NHANES 1999-2004 and Machine Learning Models.Brain and behavior · 2025Article
- 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.The journal of headache and pain · 2025Article
- Gut neuropeptide involvement in Parkinson's disease.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- Substance P release from rat dura mater is inversely correlated with CGRP release- experiments using glycerol trinitrate and anti-CGRP antibodies.The journal of headache and pain · 2025Article
- Revisiting substance P in migraine: a methodological approach inspired by anti-CGRP and anti-PACAP success.The journal of headache and pain · 2025Article
- Bidirectional substance P signaling between periodontal ligament fibroblasts and sensory neurons under mechanical stress.Frontiers in molecular neuroscience · 2025Article
- Article
- MERTK in the rat trigeminal system: a potential novel target for cluster headache?The journal of headache and pain · 2024Article
- The Role of Glial Cells in Different Phases of Migraine: Lessons from Preclinical Studies.International journal of molecular sciences · 2023Review
- Tachykinins and the potential causal factors for post-COVID-19 condition.The Lancet. Microbe · 2023Review
- PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.The journal of headache and pain · 2023Article
- Activation of Parabrachial Tachykinin 1 Neurons Counteracts Some Behaviors Mediated by Parabrachial Calcitonin Gene-related Peptide Neurons.Neuroscience · 2023Article
- Expression of the Calcitonin Receptor-like Receptor (CALCRL) in Normal and Neoplastic Tissues.International journal of molecular sciences · 2023Article
- Hemokinin-1 induces transcriptomic alterations in pain-related signaling processes in rat primary sensory neurons independent of NK1 tachykinin receptor activation.Frontiers in molecular neuroscience · 2023Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substance P (SP) and calcitonin gene-related peptide (CGRP) have both been considered potential drug candidates in migraine therapy. In recent years, CGRP receptor inhibition has been established as an effective treatment, in particular as a prophylactic for chronic migraine. Curiously, inhibition of neurokinin receptor 1 (NK1R) failed to alleviate acute migraine attacks in clinical trials, and the neurokinins were consequently abandoned as potential antimigraine candidates. The reason behind this has remained enigmatic.Utilizing immunohistochemistry and semi-quantitative cell counts the expression of neurokinins and their associated receptors was examined in the rat trigeminal ganglion.Immunohistochemistry results revealed SP co-localization in CGRP positive neurons and C-fibres, where it mainly concentrated at boutons. Neurokinin A (NKA) was observed in a population of C-fibres and small neurons where it could co-localize with SP. In contrast, neurokinin B (NKB) did not co-localize with SP and was observed in large/medium sized neurons and Aδ-fibres. All neurokinin receptors (NK1-3R) were found to be expressed in a majority of trigeminal ganglion neurons and A-fibres.The functional release of SP and CGRP in the trigeminovascular system was stimulated with either 60 mM K+ or 100 nM capsaicin and measured with an enzyme-linked immunosorbent assay (ELISA). ELISA results established that SP can be released locally from trigeminovascular system. The released SP was comparatively minor compared to the CGRP release from stimulated dura mater, trigeminal ganglion neurons and fibres. We hypothesize that SP and CGRP signalling pathways may work in tandem to exacerbate painful stimuli in the TGV system.
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