ArticleThe journal of headache and pain2025
Activation of central and peripheral transient receptor potential melastatin 8 increases susceptibility to spreading depolarization and facilitates trigeminal neuroinflammation.
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 3 papers.
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Who cites it
3 citing papers in PubMed.
- From bench to bedside: relevant animal models across the migraine attack phases.The journal of headache and pain · 2026Review
- Case Report: Resolution of Insomnia in a 32-Year-Old Male with Generalized Anxiety Disorder Following Discontinuation of Mint-Flavored Toothpaste.International medical case reports journal · 2026Article
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
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Authors and funding
9 authors.
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Abstract
backgroundTransient receptor potential melastatin 8 (TRPM8), a gene encoding a nonselective cation channel responsive to cold stimuli, has been implicated in migraine susceptibility. Despite this association, the role of TRPM8 to migraine pathogenesis remains elusive. This study aims to elucidate the potential role of TRPM8 in migraine pathophysiology.
methodsTRPM8 expression in the cortex and primary trigeminal ganglion (TG) cells was analyzed via immunostaining. The central role of TRPM8 was assessed using a spreading depolarization (SD) model, where intracerebroventricular injections or topical applications of TRPM8 agonists and antagonists were administered to rats to investigate their effects on KCl-evoked SD and SD-induced cortical inflammation. The peripheral role of TRPM8 in migraine was evaluated using primary cultures of rat TG cells by analyzing the effects of TRPM8 activation on calcitonin gene-related peptide (CGRP) expression, release, and trigeminal neuroinflammation.
resultsTRPM8 was homogeneously distributed in the cerebral cortex, predominantly co-localizing with cortical neurons. Activation of cortical TRPM8 increased the frequency of KCl-evoked SD and exacerbated SD-induced cortical inflammation. Interestingly. Interestingly, inhibition of cerebral TRPM8 had negligible effects. In TG primary cultures, TRPM8 activation upregulated CGRP expression and release and induced cyclooxygenase-2 (Cox2) upregulation via a calmodulin kinase II (CaMKII)-dependent mechanism.
conclusionsTRPM8 activation increased susceptibility to SD and facilitated the effects of CGRP and trigeminal neuroinflammation, implicating that TRPM8 may contribute to migraine pathophysiology through central and peripheral mechanisms.
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