Pharmacological evidence that spinal α2C- and, to a lesser extent, α2A-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation

Villalón, Carlos M.; Galicia-Carreón, Jorge; González‐Hernández, Abimael; Marichal‐Cancino, Bruno A.; Manrique-Maldonado, Guadalupe; Centurión, David

doi:10.1016/j.ejphar.2012.03.002

Cited by 9 publications

(4 citation statements)

References 44 publications

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“…Ergot alkaloids such as ergotamine and dihydroergotamine (DHE) have a structural resemblance with monoamines and have an affinity for serotonergic, dopaminergic, and adrenergic receptors. , Ergotamine and DHE show their antimigraine action mainly through stimulation of 5-HT 1 receptors (especially 5-HT 1B , 5-HT 1D , and 5-HT 1F subtypes) and α 1 and α 2A/2C located in intracranial blood vessels, resulting in vasoconstriction and inhibition of proinflammatory neuropeptide release. − These drugs are beneficial, but they have significant adverse consequences if overdosed, such as arterial vasospasm, mainly in peripheral arteries, resulting in cerebral infarction . Lately, triptans are the first choice of drug to abort migraine attacks and they do not have cardiovascular side effects, but they do have a tendency to produce coronary vasoconstriction. , The cardiovascular side effects of triptans resulted in the development of lasmiditan (ditans), a lipophilic 5-HT 1F agonist.…”

Section: Antimigraine Drugs: a Risk Factor For Strokementioning

confidence: 99%

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway

Raut

Singh

Sarmah

et al. 2020

ACS Chem. Neurosci.

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Migraine and stroke are common, disabling neurological conditions with several theories being proposed to explain this bidirectional relationship. Migraine is considered as a benign neurological disorder, but research has revealed a connection between migraine and stroke, predominantly those having migraine with aura (MA). Among migraineurs, females with MA are more susceptible to ischemic stroke and may have a migrainous infarction. Migrainous infarction mostly occurs in the posterior circulation of young women. Although there are several theories about the potential relationship between MA and stroke, the precise pathological process of migrainous infarction is not clear. It is assumed that cortical spreading depression (CSD) might be one of the essential factors for migrainous infarction. Other factors that may contribute to migrainous infarction may be genetic, hormonal fluctuation, hypercoagulation, and right to left cardiac shunts. Antimigraine drugs, such as ergot alkaloids and triptans, are widely used in migraine care. Still, they have been found to cause severe vasoconstriction, which may result in the development of ischemia. It is reported that patients with stroke develop migraines during the recovery phase. Both experimental and clinical data suggest that cerebral microembolism can act as a potential trigger for MA. Further studies are warranted for the treatment of migraine, which may lead to a decline in migraine-related stroke. In this present article, we have outlined various potential pathways that link migraine and stroke.

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Section: Antimigraine Drugs: a Risk Factor For Strokementioning

confidence: 99%

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway

Raut

Singh

Sarmah

et al. 2020

ACS Chem. Neurosci.

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“…This complexity may depend on the type of adrenergic receptor stimulated, the localization of the receptor (e.g., PAFs, interneurons, second-order neurons), and the type of nociceptive input. For example, at the spinal trigeminal level, both α 2A -, and α 2C -adrenoceptors seem to inhibit nociceptive transmission ( Villalón et al, 2012 ). More recently, it has been suggested that at the spinal cord level, the noradrenergic system elicits a fine-tunning of nociception by activation of α 1 -or α 2 -adrenoceptors; indeed, they proposed that spinal α 2 -adrenoceptors located presynaptically in the noradrenergic projections from the ventral LC can be modulating the firing of GABAergic interneurons (see Suppl Fig 2 in Kucharczyk et al (2022) ).…”

Section: Discussionmentioning

confidence: 99%

The differential in vivo contribution of spinal α2A- and α2C-adrenoceptors in tonic and acute evoked nociception in the rat

et al. 2022

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Spinal α2-adrenoceptor induces analgesia by neuronal inhibition of primary afferent fibers. This family receptor coupled to Gi/o proteins can be subdivided into three functional subtypes: α2A, α2B, and α2C-adrenoceptors, and current evidence on spinal analgesia supports the relevance of α2A and seems to exclude the role of α2B, but the functional contribution of α2C-adrenoceptors remains elusive. The present study was designed to pharmacologically dissect the contribution of spinal α2-adrenoceptor subtypes modulating tonic or acute peripheral nociception. Using male Wistar rats, we analyzed the effect of spinal clonidine (a non-selective α2A/α2B/α2C-adrenoceptor agonist) and/or selective subtype α2-adrenoceptor antagonists on: 1) tonic nociception induced by subcutaneous formalin (flinching behavior) or 2) acute nociception induced by peripheral electrical stimulus in in vivo extracellular recordings of spinal dorsal horn second-order wide dynamic range (WDR) neurons. Clonidine inhibited the nocifensive behavior induced by formalin, an effect blocked by BRL 44408 (α2A-adrenoceptor antagonist) but not by imiloxan (α2B-adrenoceptor antagonist) or JP 1302 (α2C-adrenoceptor antagonist). Similarly, spinal BRL 44408 reversed the clonidine-induced inhibition of nociceptive WDR activity. Interestingly, spinal JP 1302 per se produced behavioral antinociception (an effect blocked by bicuculline, a preferent GABAA channel blocker), but no correlation was found with the electrophysiological experiments. These data imply that, at the spinal level, 1) presynaptic α2A-adrenoceptor activation produces antinociception during acute or tonic nociceptive stimuli; and 2) under tonic nociceptive (inflammatory) input, spinal α2C-adrenoceptors are pronociceptive, probably by the inactivation of GABAergic transmission. This result supports a differential role of α2A and α2C-adrenoceptors modulating nociception.

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“…Hence, peripheral release of CGRP (which induces vasodilatation) into the trigeminovascular system is regulated by several mechanisms of neuromodulation at the neurovascular junction and almost all these systems and receptors are also modulating the afferent input to the trigeminal nucleus [188]. Examples of the above are the ergots (5-HT 1 , α 2 -adrenergic, and D 2 -like receptor agonists) and triptans (selective 5-HT 1B/1D/1F receptor agonist) [186, 189–191]. In fact, treatments to specifically block the function of CGRP receptors are the targets of the pharmacological therapies under clinical review which promise to decrease the side effects of classic antimigraine drugs (i.e., cardiovascular effects).…”

Section: The Role Of Cgrp On Some Vascular-related Diseasesmentioning

confidence: 99%

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

González‐Hernández

Marichal‐Cancino

Lozano-Cuenca

et al. 2016

BioMed Research International

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Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP), the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor). This receptor is an atypical G-protein coupled receptor (GPCR) composed of three functional proteins: (i) the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein), (ii) the activity-modifying protein type 1 (RAMP1), and (iii) a receptor component protein (RCP). Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia). The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

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Pharmacological evidence that spinal α2C- and, to a lesser extent, α2A-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation

Cited by 9 publications

References 44 publications

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway

The differential in vivo contribution of spinal α2A- and α2C-adrenoceptors in tonic and acute evoked nociception in the rat

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

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