Utilize este identificador para referenciar este registo:
https://hdl.handle.net/10216/114500
Autor(es): | Kilinc, E Guerrero-Toro, C Zakharov, A Vitale, C Gubert-Olive, M Koroleva, K Timonina, A Luz, LL Shelukhina, I Giniatullina, R Tore, F Safronov, BV Giniatullin, R |
Título: | Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain |
Editor: | Elsevier |
Data de publicação: | 2017 |
Resumo: | Serotonergic mechanisms play a central role in migraine pathology. However, the region-specific effects of serotonin (5-HT) mediated via multiple types of receptors in the nociceptive system are poorly understood. Using extracellular and patch-clamp recordings, we studied the action of 5-HT on the excitability of peripheral and central terminals of trigeminal afferents. 5-HT evoked long-lasting TTX-sensitive firing in the peripheral terminals of meningeal afferents, the origin site of migraine pain. Cluster analysis revealed that in majority of nociceptive fibers 5-HT induced either transient or persistent spiking activity with prevailing delta and theta rhythms. The 5-HT3-receptor antagonist MDL-72222 or 5-HT1B/D-receptor antagonist GR127935 largely reduced, but their combination completely prevented the excitatory pro-nociceptive action of 5-HT. The 5-HT3 agonist mCPBG activated spikes in MDL-72222-dependent manner but the 5HT-1 receptor agonist sumatriptan did not affect the nociceptive firing. 5-HT also triggered peripheral CGRP release in meninges, which was blocked by MDL-72222.5-HT evoked fast membrane currents and Ca2+ transients in a fraction of trigeminal neurons. Immunohistochemistry showed expression of 5-HT3A receptors in fibers innervating meninges. Endogenous release of 5-HT from degranulated mast cells increased nociceptive firing. Low pH but not histamine strongly activated firing. 5-HT reduced monosynaptic inputs from trigeminal Aδ- and C-afferents to the upper cervical lamina I neurons and this effect was blocked by MDL-72222. Consistent with central inhibitory effect, 5-HT reduced CGRP release in the brainstem slices. In conclusion, 5-HT evokes powerful pro-nociceptive peripheral and anti-nociceptive central effects in trigeminal system transmitting migraine pain. |
Assunto: | 5-HT3 receptor Migraine Serotonin Spike Trigeminal nerve |
URI: | http://hdl.handle.net/10216/114500 |
Fonte: | Neuropharmacology, vol. 116, p. 160-173 |
Informação Relacionada: | Códigos não localizados |
Tipo de Documento: | Artigo em Revista Científica Internacional |
Condições de Acesso: | openAccess |
Aparece nas coleções: | I3S - Artigo em Revista Científica Internacional |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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10.1016 j.neuropharm.2016.12.024.pdf | 1.37 MB | Adobe PDF | Ver/Abrir | |
10.1016 j.neuropharm.2016.12.024- S.I.pdf | 247.43 kB | Adobe PDF | Ver/Abrir |
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