High‐dose phenylephrine increases meningeal blood flow through TRPV1 receptor activation and release of calcitonin gene‐related peptide

Dux, Mária; Babeș, Alexandru; Manchen, Jessica; Sertel-Nakajima, Julika; Vogler, Birgit; Schramm, Jana; Meßlinger, Karl

doi:10.1002/ejp.1495

Cited by 9 publications

(10 citation statements)

References 51 publications

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“…Alternatively, Dux et al. have recently reported that phenylephrine causes trigeminal nociception and increases meningeal blood flow through TRPV1 receptor activation and release of CGRP (83). Likewise, endothelin-1 on its own can induce pain-like behaviors in rodents (84) and can sensitize nociceptors and enhance release of glutamate in sensory neurons (85).…”

Section: Discussionmentioning

confidence: 99%

Vascular actions of peripheral CGRP in migraine-like photophobia in mice

et al. 2020

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Background Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice. Methods Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay. Results Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion. Conclusion We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

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Section: Discussionmentioning

confidence: 99%

Vascular actions of peripheral CGRP in migraine-like photophobia in mice

et al. 2020

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“…Results obtained in trigeminal neurons of TRPV1-deficient animals supported this observation. Phenylephrine-induced calcium transients and CGRP release were abolished in trigeminal ganglion neurons of TRPV1-deficient animals [36].…”

Section: Medication-induced Trigeminal Nociception and Painmentioning

confidence: 89%

“…Trigeminal ganglia in situ or cultivated trigeminal ganglion cells from rodents are frequently used to measure the release of substances following stimulation with noxious agents that target TRPV1 and TRPA1 receptors [35,36]. Particularly quantification of CGRP release from trigeminal ganglia or trigeminal cell cultures induced by capsaicin is regarded as a parameter for trigeminal activation and sensitization [37,38].…”

Section: Neuropeptide Releasementioning

confidence: 99%

“…Finally, trigeminal ganglion cell cultures have frequently been used to study the molecular properties of neurons and responses to endogenous and environmental mediators using calcium imaging [36,37]. Agonists and antagonists specifically targeting TRP receptor channels are employed to find out the role of TRPs in the neuronal activation [40].…”

Section: Calcium Imagingmentioning

confidence: 99%

“…Drugs used for other purposes than headache therapy may alter the sensitivity of nociceptors leading to uncomfortable or painful sensations upon administration. The α1-adrenoceptor agonist phenylephrine used at high concentrations as a mydriatic agent and for the treatment of nasal congestion may induce local burning sensation or headache as adverse side effect [36]. Recent experiments revealed that high concentrations of phenylephrine activate trigeminal neurons in rodent models of trigeminal nociception.…”

Section: Medication-induced Trigeminal Nociception and Painmentioning

confidence: 99%

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TRP Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches

Dux

Rosta

Meßlinger

2020

IJMS

Self Cite

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Pain in trigeminal areas is driven by nociceptive trigeminal afferents. Transduction molecules, among them the nonspecific cation channels transient receptor potential vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1), which are activated by endogenous and exogenous ligands, are expressed by a significant population of trigeminal nociceptors innervating meningeal tissues. Many of these nociceptors also contain vasoactive neuropeptides such as calcitonin gene-related peptide (CGRP) and substance P. Release of neuropeptides and other functional properties are frequently examined using the cell bodies of trigeminal neurons as models of their sensory endings. Pathophysiological conditions cause phosphorylation, increased expression and trafficking of transient receptor potential (TRP) channels, neuropeptides and other mediators, which accelerate activation of nociceptive pathways. Since nociceptor activation may be a significant pathophysiological mechanism involved in both peripheral and central sensitization of the trigeminal nociceptive pathway, its contribution to the pathophysiology of primary headaches is more than likely. Metabolic disorders and medication-induced painful states are frequently associated with TRP receptor activation and may increase the risk for primary headaches.

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A TRiP Through the Roles of Transient Receptor Potential Cation Channels in Type 2 Upper Airway Inflammation

Backaert

Steelant

Hellings

et al. 2021

Curr Allergy Asthma Rep

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Purpose of Review Despite their high prevalence, the pathophysiology of allergic rhinitis (AR) and chronic rhinosinusitis (CRS) remains unclear. Recently, transient receptor potential (TRP) cation channels emerged as important players in type 2 upper airway inflammatory disorders. In this review, we aim to discuss known and yet to be explored roles of TRP channels in the pathophysiology of AR and CRS with nasal polyps. Recent Findings TRP channels participate in a plethora of cellular functions and are expressed on T cells, mast cells, respiratory epithelial cells, and sensory neurons of the upper airways. In chronic upper airway inflammation, TRP vanilloid 1 is mostly studied in relation to nasal hyperreactivity. Several other TRP channels such as TRP vanilloid 4, TRP ankyrin 1, TRP melastatin channels, and TRP canonical channels also have important functions, rendering them potential targets for therapy. Summary The role of TRP channels in type 2 inflammatory upper airway diseases is steadily being uncovered and increasingly recognized. Modulation of TRP channels may offer therapeutic perspectives.

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High‐dose phenylephrine increases meningeal blood flow through TRPV1 receptor activation and release of calcitonin gene‐related peptide

Cited by 9 publications

References 51 publications

Vascular actions of peripheral CGRP in migraine-like photophobia in mice

Vascular actions of peripheral CGRP in migraine-like photophobia in mice

TRP Channels in the Focus of Trigeminal Nociceptor Sensitization Contributing to Primary Headaches

A TRiP Through the Roles of Transient Receptor Potential Cation Channels in Type 2 Upper Airway Inflammation

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