dc.contributor.author |
Kilinc E. |
|
dc.contributor.author |
Guerrero-Toro C. |
|
dc.contributor.author |
Zakharov A. |
|
dc.contributor.author |
Vitale C. |
|
dc.contributor.author |
Gubert-Olive M. |
|
dc.contributor.author |
Koroleva K. |
|
dc.contributor.author |
Timonina A. |
|
dc.contributor.author |
Luz L. |
|
dc.contributor.author |
Shelukhina I. |
|
dc.contributor.author |
Giniatullina R. |
|
dc.contributor.author |
Tore F. |
|
dc.contributor.author |
Safronov B. |
|
dc.contributor.author |
Giniatullin R. |
|
dc.date.accessioned |
2018-09-19T22:03:46Z |
|
dc.date.available |
2018-09-19T22:03:46Z |
|
dc.date.issued |
2017 |
|
dc.identifier.issn |
0028-3908 |
|
dc.identifier.uri |
https://dspace.kpfu.ru/xmlui/handle/net/144645 |
|
dc.description.abstract |
© 2016 Elsevier LtdSerotonergic 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. |
|
dc.relation.ispartofseries |
Neuropharmacology |
|
dc.subject |
5-HT3 receptor |
|
dc.subject |
Migraine |
|
dc.subject |
Serotonin |
|
dc.subject |
Spike |
|
dc.subject |
Trigeminal nerve |
|
dc.title |
Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain |
|
dc.type |
Article |
|
dc.relation.ispartofseries-volume |
116 |
|
dc.collection |
Публикации сотрудников КФУ |
|
dc.relation.startpage |
160 |
|
dc.source.id |
SCOPUS00283908-2017-116-SID85008312080 |
|