Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain
Peripheral mechanisms of primary headaches such as a migraine remain unclear. Meningeal afferents surrounded by multiple mast cells have been suggested as a major source of migraine pain. Extracellular ATP released during migraine attacks is a likely candidate for activating meningeal afferents via...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00195/full |
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| author | Ksenia Koroleva Ksenia Koroleva Oleg Gafurov Valeriia Guselnikova Valeriia Guselnikova Dilyara Nurkhametova Dilyara Nurkhametova Raisa Giniatullina Guzel Sitdikova Olli S. Mattila Perttu J. Lindsberg Tarja Maarit Malm Rashid Giniatullin Rashid Giniatullin |
| author_facet | Ksenia Koroleva Ksenia Koroleva Oleg Gafurov Valeriia Guselnikova Valeriia Guselnikova Dilyara Nurkhametova Dilyara Nurkhametova Raisa Giniatullina Guzel Sitdikova Olli S. Mattila Perttu J. Lindsberg Tarja Maarit Malm Rashid Giniatullin Rashid Giniatullin |
| author_sort | Ksenia Koroleva |
| collection | DOAJ |
| description | Peripheral mechanisms of primary headaches such as a migraine remain unclear. Meningeal afferents surrounded by multiple mast cells have been suggested as a major source of migraine pain. Extracellular ATP released during migraine attacks is a likely candidate for activating meningeal afferents via neuronal P2X receptors. Recently, we showed that ATP also increased degranulation of resident meningeal mast cells (Nurkhametova et al., 2019). However, the contribution of ATP-induced mast cell degranulation in aggravating the migraine pain remains unknown. Here we explored the role of meningeal mast cells in the pro-nociceptive effects of extracellular ATP. The impact of mast cells on ATP mediated activation of peripheral branches of trigeminal nerves was measured electrophysiologically in the dura mater of adult wild type (WT) or mast cell deficient mice. We found that a spontaneous spiking activity in the meningeal afferents, at baseline level, did not differ in two groups. However, in WT mice, meningeal application of ATP dramatically (24.6-fold) increased nociceptive firing, peaking at frequencies around 10 Hz. In contrast, in mast cell deficient animals, ATP-induced excitation was significantly weaker (3.5-fold). Application of serotonin to meninges in WT induced strong spiking. Moreover, in WT mice, the 5-HT3 antagonist MDL-7222 inhibited not only serotonin but also the ATP induced nociceptive firing. Our data suggest that extracellular ATP activates nociceptive firing in meningeal trigeminal afferents via amplified degranulation of resident mast cells in addition to direct excitatory action on the nerve terminals. This highlights the importance of mast cell degranulation via extracellular ATP, in aggravating the migraine pain. |
| first_indexed | 2024-04-13T04:30:32Z |
| format | Article |
| id | doaj.art-828fe8416f824bfca30a191119070928 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-13T04:30:32Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-828fe8416f824bfca30a1911190709282022-12-22T03:02:20ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-05-011310.3389/fncel.2019.00195460735Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine PainKsenia Koroleva0Ksenia Koroleva1Oleg Gafurov2Valeriia Guselnikova3Valeriia Guselnikova4Dilyara Nurkhametova5Dilyara Nurkhametova6Raisa Giniatullina7Guzel Sitdikova8Olli S. Mattila9Perttu J. Lindsberg10Tarja Maarit Malm11Rashid Giniatullin12Rashid Giniatullin13Laboratory of Neurobiology, Kazan Federal University, Kazan, RussiaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandDepartment of General and Special Morphology, Institute of Experimental Medicine, Saint Petersburg, RussiaLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaDepartment of Neurology and Clinical Neurosciences, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandDepartment of Neurology and Clinical Neurosciences, University of Helsinki and Helsinki University Hospital, Helsinki, FinlandA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandLaboratory of Neurobiology, Kazan Federal University, Kazan, RussiaA. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandPeripheral mechanisms of primary headaches such as a migraine remain unclear. Meningeal afferents surrounded by multiple mast cells have been suggested as a major source of migraine pain. Extracellular ATP released during migraine attacks is a likely candidate for activating meningeal afferents via neuronal P2X receptors. Recently, we showed that ATP also increased degranulation of resident meningeal mast cells (Nurkhametova et al., 2019). However, the contribution of ATP-induced mast cell degranulation in aggravating the migraine pain remains unknown. Here we explored the role of meningeal mast cells in the pro-nociceptive effects of extracellular ATP. The impact of mast cells on ATP mediated activation of peripheral branches of trigeminal nerves was measured electrophysiologically in the dura mater of adult wild type (WT) or mast cell deficient mice. We found that a spontaneous spiking activity in the meningeal afferents, at baseline level, did not differ in two groups. However, in WT mice, meningeal application of ATP dramatically (24.6-fold) increased nociceptive firing, peaking at frequencies around 10 Hz. In contrast, in mast cell deficient animals, ATP-induced excitation was significantly weaker (3.5-fold). Application of serotonin to meninges in WT induced strong spiking. Moreover, in WT mice, the 5-HT3 antagonist MDL-7222 inhibited not only serotonin but also the ATP induced nociceptive firing. Our data suggest that extracellular ATP activates nociceptive firing in meningeal trigeminal afferents via amplified degranulation of resident mast cells in addition to direct excitatory action on the nerve terminals. This highlights the importance of mast cell degranulation via extracellular ATP, in aggravating the migraine pain.https://www.frontiersin.org/article/10.3389/fncel.2019.00195/fullATP5-HT3mast cellspainmigraine |
| spellingShingle | Ksenia Koroleva Ksenia Koroleva Oleg Gafurov Valeriia Guselnikova Valeriia Guselnikova Dilyara Nurkhametova Dilyara Nurkhametova Raisa Giniatullina Guzel Sitdikova Olli S. Mattila Perttu J. Lindsberg Tarja Maarit Malm Rashid Giniatullin Rashid Giniatullin Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain Frontiers in Cellular Neuroscience ATP 5-HT3 mast cells pain migraine |
| title | Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain |
| title_full | Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain |
| title_fullStr | Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain |
| title_full_unstemmed | Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain |
| title_short | Meningeal Mast Cells Contribute to ATP-Induced Nociceptive Firing in Trigeminal Nerve Terminals: Direct and Indirect Purinergic Mechanisms Triggering Migraine Pain |
| title_sort | meningeal mast cells contribute to atp induced nociceptive firing in trigeminal nerve terminals direct and indirect purinergic mechanisms triggering migraine pain |
| topic | ATP 5-HT3 mast cells pain migraine |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00195/full |
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