Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists
Abstract Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-021-01383-8 |
| _version_ | 1819006743240245248 |
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| author | G. Krivoshein E. A. Tolner van den Maagdenberg AMJM R. A. Giniatullin |
| author_facet | G. Krivoshein E. A. Tolner van den Maagdenberg AMJM R. A. Giniatullin |
| author_sort | G. Krivoshein |
| collection | DOAJ |
| description | Abstract Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes. Methods Ten- to 13-week-old male and female wildtype (WT) C57BL/6 J mice were used. Nociceptive spikes were recorded directly from nerve terminals in the meninges in the hemiskull preparations. Results Selective agonists of TRPM3 channels profoundly activated peripheral trigeminal nerve fibres in mouse meninges. A sex difference was observed for nociceptive firing induced by either PregS or CIM0216, both agonists of TRPM3 channels, with the induced firing being particularly prominent for female mice. Application of Yoda1, an agonist of Piezo1 channels, or capsaicin activating TRPV1 channels, although also leading to increased nociceptive firing of meningeal fibres, did not reveal a sex difference. Cluster analyses of spike activities indicated a massive and long-lasting activation of TRPM3 channels with preferential induction of large-amplitude spikes in female mice. Additional spectral analysis revealed a dominant contribution of spiking activity in the α- and β-ranges following TRPM3 agonists in female mice. Conclusions Together, we revealed a specific mechanosensitive profile of nociceptive firing in females and suggest TRPM3 channels as a potential novel candidate for the generation of migraine pain, with particular relevance to females. |
| first_indexed | 2024-12-21T00:13:32Z |
| format | Article |
| id | doaj.art-59649d1e58924ebab5b63313af98de9d |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-21T00:13:32Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-59649d1e58924ebab5b63313af98de9d2022-12-21T19:22:17ZengBMCThe Journal of Headache and Pain1129-23691129-23772022-01-0123111210.1186/s10194-021-01383-8Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonistsG. Krivoshein0E. A. Tolner1van den Maagdenberg AMJM2R. A. Giniatullin3A.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandDepartment of Human Genetics, Leiden University Medical CenterDepartment of Human Genetics, Leiden University Medical CenterA.I.Virtanen Institute for Molecular Sciences, University of Eastern FinlandAbstract Background Migraine is a common brain disorder that predominantly affects women. Migraine pain seems mediated by the activation of mechanosensitive channels in meningeal afferents. Given the role of transient receptor potential melastatin 3 (TRPM3) channels in mechanical activation, as well as hormonal regulation, these channels may play a role in the sex difference in migraine. Therefore, we investigated whether nociceptive firing induced by TRPM3 channel agonists in meningeal afferents was different between male and female mice. In addition, we assessed the relative contribution of mechanosensitive TRPM3 channels and that of mechanosensitive Piezo1 channels and transient receptor potential vanilloid 1 (TRPV1) channels to nociceptive firing relevant to migraine in both sexes. Methods Ten- to 13-week-old male and female wildtype (WT) C57BL/6 J mice were used. Nociceptive spikes were recorded directly from nerve terminals in the meninges in the hemiskull preparations. Results Selective agonists of TRPM3 channels profoundly activated peripheral trigeminal nerve fibres in mouse meninges. A sex difference was observed for nociceptive firing induced by either PregS or CIM0216, both agonists of TRPM3 channels, with the induced firing being particularly prominent for female mice. Application of Yoda1, an agonist of Piezo1 channels, or capsaicin activating TRPV1 channels, although also leading to increased nociceptive firing of meningeal fibres, did not reveal a sex difference. Cluster analyses of spike activities indicated a massive and long-lasting activation of TRPM3 channels with preferential induction of large-amplitude spikes in female mice. Additional spectral analysis revealed a dominant contribution of spiking activity in the α- and β-ranges following TRPM3 agonists in female mice. Conclusions Together, we revealed a specific mechanosensitive profile of nociceptive firing in females and suggest TRPM3 channels as a potential novel candidate for the generation of migraine pain, with particular relevance to females.https://doi.org/10.1186/s10194-021-01383-8MigraineTRPM3NociceptionSex-dependencePregnenolone sulfateCIM0216 |
| spellingShingle | G. Krivoshein E. A. Tolner van den Maagdenberg AMJM R. A. Giniatullin Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists The Journal of Headache and Pain Migraine TRPM3 Nociception Sex-dependence Pregnenolone sulfate CIM0216 |
| title | Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists |
| title_full | Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists |
| title_fullStr | Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists |
| title_full_unstemmed | Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists |
| title_short | Migraine-relevant sex-dependent activation of mouse meningeal afferents by TRPM3 agonists |
| title_sort | migraine relevant sex dependent activation of mouse meningeal afferents by trpm3 agonists |
| topic | Migraine TRPM3 Nociception Sex-dependence Pregnenolone sulfate CIM0216 |
| url | https://doi.org/10.1186/s10194-021-01383-8 |
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