Sumatriptan inhibits the electrophysiological activity of ASICs in rat trigeminal ganglion neurons

Guo, Longhua; Zhao, Ling; Ming, Pinghong; Li, Hong; Ai-sheng, Liu; Li, Rukai

doi:10.1016/j.ejphar.2018.10.013

Cited by 15 publications

(7 citation statements)

References 39 publications

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“…Targeting mechanisms that lead to cAMP release leads to dilation of extracerebral arteries and migraine attacks in a high proportion of patients, which can be inhibited by sumatriptan (29,47). Sumatriptan inhibits the cAMP and protein kinase A (PKA) signaling pathway (48)(49)(50)(51), and administration of subcutaneous sumatriptan in PACAP38-induced migraine has been found to attenuate headache along with constricting STA and MMA, but not MCA (31), suggesting a peripheral site of action of sumatriptan. In the present study, intravenous sumatriptan constricted the pre-dilated STA during the first 2 h, probably via the 5-HT 1B receptors.…”

Section: Vascular Inhibitionmentioning

confidence: 99%

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial

et al. 2021

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Objective To determine whether early treatment with sumatriptan can prevent PACAP38-induced migraine attacks. Methods A total of 37 patients with migraine without aura were enrolled between July 2018 to December 2019. All patients received an intravenous infusion of 10 picomole/kg/min of PACAP38 over 20 min followed by an intravenous infusion of 4 mg sumatriptan or placebo over 10 min on two study days in a randomised, double-blind, placebo-controlled, crossover study. Results Of 37 patients enrolled, 26 (70.3%) completed the study and were included in analyses. Of the 26 patients, four (15%) developed a PACAP38-induced migraine attack on sumatriptan and 11 patients (42%) on placebo ( p = 0.016). There were no differences in area under the curve for headache intensity between sumatriptan (mean AUC 532) and placebo (mean AUC 779) ( p = 0.35). Sumatriptan significantly constricted the PACAP38-dilated superficial temporal artery immediately after infusion (T30) compared with infusion of placebo ( p < 0.001). Conclusions and relevance: Early treatment with intravenously administered sumatriptan prevented PACAP38-induced migraine. Prevention of migraine attacks was associated with vasoconstriction by sumatriptan in the earliest phases of PACAP provocation. These results suggest that sumatriptan prevents PACAP38-induced migraine by modulation of nociceptive transmission within the trigeminovascular system. Trial Registration: ClinicalTrials.gov (NCT03881644).

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Section: Vascular Inhibitionmentioning

confidence: 99%

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial

et al. 2021

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“…It is co‐expressed with calcitonin gene‐related peptide (CGRP) in the rat trigeminal ganglion (Ichikawa & Sugimoto, ), where decreased pH results in CGRP release (Durham & Masterson, ). Pharmacologically the anti‐migraine therapeutic agent, the 5‐HT 1B/1D agonist sumatriptan, also inhibits the activity of ASICs in the rat trigeminal ganglion (Guo et al, ), while an ASIC‐sensitive proton‐mediated mechanism for the release of CGRP has been demonstrated. Given the therapeutic utility of the triptans (Ong & De Felice, ) and targeted modulation of CGRP signalling (Goadsby et al, ), ASIC modulation may represent a novel target with important translational implications.…”

Section: Introductionmentioning

confidence: 99%

Acid‐sensing ion channel 3 blockade inhibits durovascular and nitric oxide‐mediated trigeminal pain

Holton

Strother

Dripps

et al. 2020

British J Pharmacology

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Background and Purpose:There is a major unmet need to develop new therapies for migraine. We have previously demonstrated the therapeutic potential of the acidsensing ion channel (ASIC) blockade in migraine, via an ASIC1 mechanism. ASIC3 is expressed in the trigeminal ganglion and its response is potentiated by NO that can trigger migraine attacks in patients. Thus we sought to explore the potential therapeutic effect of ASIC3 blockade in migraine. Experimental Approach:To investigate this, we utilised validated electrophysiological and behavioural rodent preclinical models. In rats, ASIC3 blockade using APETx2 (50 or 100 μgÁkg −1 , i.v.) was measured by using durovascular and NO-evoked trigeminal nociceptive responses along with cortical spreading depression models. In mice, we sought to determine if periorbital mechanical sensitivity, induced by acute nitroglycerin (10 mgÁkg −1 , i.p.), was attenuated by APETx2 (230 μgÁkg −1 , i.p.), as well as latent sensitisation induced by bright light stress in a chronic nitroglycerin model. Key Results: Here, we show that the ASIC3 blocker APETx2 inhibits durovascularevoked and NO-induced sensitisation of trigeminal nociceptive responses in rats. In agreement, acute and chronic periorbital mechanosensitivity induced in mice by nitroglycerin and subsequent bright light stress-evoked latent sensitivity as a model of chronic migraine are all reversed by APETx2. Conclusion and Implications:These results support the development of specific ASIC3 or combined ASIC1/3 blockers for migraine-related pain and point to a potential role for ASIC-dependent NO-mediated attack triggering. This has key implications for migraine, given the major unmet need for novel therapeutic targets.Abbreviations: ASIC, acid-sensing ion channel; BLS, bright light stress; CSD, cortical spreading depression; MMA, the middle meningeal artery; NTG, nitroglycerin; SNP, sodium nitroprusside; TNC, trigeminal nucleus caudalis.Christopher M. Holton and Lauren C. Strother contributed equally to this work.

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“…12,13 Acid-sensing ion channels are expressed in various cells of the body, especially in the central and peripheral nervous systems. 14 Importantly, ASIC1 is one of the targets of miR-485-5p predicted by bioinformatics, and recent studies have demonstrated the influence of ASIC channels on the symptoms of inflammatory pain, 15,16 whose pathophysiological mechanism is related to changes in pH. 1 However, the regulation of ASIC1 in inflammatory pain remains unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>Decreased MiR-485-5p Contributes to Inflammatory Pain Through Post-Transcriptional Upregulation of ASIC1 in Rat Dorsal Root Ganglion</p>

Xu¹,

Wu²,

Zhang³

et al. 2020

JPR

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Sumatriptan inhibits the electrophysiological activity of ASICs in rat trigeminal ganglion neurons

Cited by 15 publications

References 39 publications

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial

Early treatment with sumatriptan prevents PACAP38-induced migraine: A randomised clinical trial

Acid‐sensing ion channel 3 blockade inhibits durovascular and nitric oxide‐mediated trigeminal pain

<p>Decreased MiR-485-5p Contributes to Inflammatory Pain Through Post-Transcriptional Upregulation of ASIC1 in Rat Dorsal Root Ganglion</p>

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