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dc.contributor.advisorFranzblau, Carlen_US
dc.contributor.advisorMao, Jianrenen_US
dc.contributor.authorDoheny, Jasonen_US
dc.date.accessioned2020-06-17T15:33:20Z
dc.date.available2020-06-17T15:33:20Z
dc.date.issued2020
dc.identifier.urihttps://hdl.handle.net/2144/41212
dc.description.abstractTrigeminal neuropathic pain (TNP) is a condition that occurs when one or more branches of the trigeminal nerve are insulted. Trigeminal neuropathic pain has been shown to be refractory to treatment. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both the peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain, however, the impact of thalamic HCN channel activity on TNP has yet to be elucidated. In this report, we used a chronic constriction of the distal infraorbital nerve (dIoN-CCI) to induce TNP in rats. By infusing HCN channel blockers into the ventral posteromedial (VPM) nucleus of the thalamus in dIoN-CCI rats, we demonstrated that inhibition of HCN channel activity ameliorated TNP. We found that the HCN blocker ZD7288 and the clinical drug ivabradine dose-dependently attenuated both evoked and none-evoked nociceptive behaviors in dIoN-CCI rats. Electrophysiological measurements showed the expression of HCN current (Ih) in the thalamocortical neurons in the VPM was sensitive to the HCN channel modulator cyclic adenosine monophosphate (cAMP), suggesting a contribution of the HCN2 subunit in thalamic HCN current. In the thalamus, surface expression of the HCN2 subunit was increased in dIoN-CCI rats. Taken together, we propose that an increase in HCN channel activity in the thalamus in the ascending nociceptive pathway contributed to trigeminal neuropathic pain.en_US
dc.language.isoen_US
dc.subjectMedicineen_US
dc.subjectdIoN-CCIen_US
dc.subjectHCN channelen_US
dc.subjectNeuropathic painen_US
dc.subjectRatsen_US
dc.subjectThalamusen_US
dc.subjectTrigeminal neuralgiaen_US
dc.titleTrigeminal neuropathic pain in rats: a role for thalamic hyperpolarization-activated cyclic nucleotide-gated channel activityen_US
dc.typeThesis/Dissertationen_US
dc.date.updated2020-06-16T22:08:01Z
etd.degree.nameMaster of Scienceen_US
etd.degree.levelmastersen_US
etd.degree.disciplineMedical Sciencesen_US
etd.degree.grantorBoston Universityen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-8341-5460


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