Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model
Abstract Background Preceding studies have reported the association of chronic neuropathic orofacial pain with altered ongoing function in the ventrolateral periaqueductal gray (vlPAG). However, its role in trigeminal neuralgia (TN) lacks attention. We here reported the aspect that vlPAG neurons pla...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | The Journal of Headache and Pain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s10194-021-01257-z |
| _version_ | 1818601815705387008 |
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| author | K. C. Elina Byeong Ho Oh Jaisan Islam Soochong Kim Young Seok Park |
| author_facet | K. C. Elina Byeong Ho Oh Jaisan Islam Soochong Kim Young Seok Park |
| author_sort | K. C. Elina |
| collection | DOAJ |
| description | Abstract Background Preceding studies have reported the association of chronic neuropathic orofacial pain with altered ongoing function in the ventrolateral periaqueductal gray (vlPAG). However, its role in trigeminal neuralgia (TN) lacks attention. We here reported the aspect that vlPAG neurons play in TN nociceptive processing by employing excitatory neuron-specific optogenetic approaches. Methods TN was generated via unilateral infraorbital nerve chronic constriction in Sprague Dawley rats which induced mechanical and thermal pain sensitivity in air puff and acetone test, respectively. Channelrhodopsin conjugated virus with CamKIIα promoter was used to specifically activate the excitatory vlPAG neuronal population by optogenetic stimulation and in vivo microdialysis was done to determine its effect on the excitatory-inhibitory balance. In vivo extracellular recordings from ventral posteromedial (VPM) thalamus were assessed in response to vlPAG optogenetic stimulation. Depending on the experimental terms, unpaired student’s t test and two-way analysis of variance (ANOVA) were used for statistical analysis. Results We observed that optogenetic activation of vlPAG subgroup neurons markedly improved pain hypersensitivity in reflexive behavior tests which was also evident on microdialysis analysis with increase glutamate concentration during stimulation period. Decreased mean firing and burst rates were evident in VPM thalamic electrophysiological recordings during the stimulation period. Overall, our results suggest the optogenetic activation of vlPAG excitatory neurons in a TN rat model has pain ameliorating effect. Conclusions This article presents the prospect of pain modulation in trigeminal pain pathway via optogenetic activation of vlPAG excitatory neurons in rat model. This outlook could potentially assist vlPAG insight and its optogenetic approach in trigeminal neuropathic pain which aid clinicians endeavoring towards enhanced pain relief therapy in trigeminal neuralgia patients. |
| first_indexed | 2024-12-16T12:57:23Z |
| format | Article |
| id | doaj.art-5f3f2eea9ffd410ea18b5a9dba7cbb50 |
| institution | Directory Open Access Journal |
| issn | 1129-2369 1129-2377 |
| language | English |
| last_indexed | 2024-12-16T12:57:23Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | The Journal of Headache and Pain |
| spelling | doaj.art-5f3f2eea9ffd410ea18b5a9dba7cbb502022-12-21T22:30:59ZengBMCThe Journal of Headache and Pain1129-23691129-23772021-05-0122111410.1186/s10194-021-01257-zActivation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat modelK. C. Elina0Byeong Ho Oh1Jaisan Islam2Soochong Kim3Young Seok Park4Department of Neuroscience, College of Medicine, Chungbuk National UniversityDepartment of Neuroscience, College of Medicine, Chungbuk National UniversityDepartment of Neuroscience, College of Medicine, Chungbuk National UniversityDepartment of Veterinary Medicine, Chungbuk National UniversityDepartment of Neuroscience, College of Medicine, Chungbuk National UniversityAbstract Background Preceding studies have reported the association of chronic neuropathic orofacial pain with altered ongoing function in the ventrolateral periaqueductal gray (vlPAG). However, its role in trigeminal neuralgia (TN) lacks attention. We here reported the aspect that vlPAG neurons play in TN nociceptive processing by employing excitatory neuron-specific optogenetic approaches. Methods TN was generated via unilateral infraorbital nerve chronic constriction in Sprague Dawley rats which induced mechanical and thermal pain sensitivity in air puff and acetone test, respectively. Channelrhodopsin conjugated virus with CamKIIα promoter was used to specifically activate the excitatory vlPAG neuronal population by optogenetic stimulation and in vivo microdialysis was done to determine its effect on the excitatory-inhibitory balance. In vivo extracellular recordings from ventral posteromedial (VPM) thalamus were assessed in response to vlPAG optogenetic stimulation. Depending on the experimental terms, unpaired student’s t test and two-way analysis of variance (ANOVA) were used for statistical analysis. Results We observed that optogenetic activation of vlPAG subgroup neurons markedly improved pain hypersensitivity in reflexive behavior tests which was also evident on microdialysis analysis with increase glutamate concentration during stimulation period. Decreased mean firing and burst rates were evident in VPM thalamic electrophysiological recordings during the stimulation period. Overall, our results suggest the optogenetic activation of vlPAG excitatory neurons in a TN rat model has pain ameliorating effect. Conclusions This article presents the prospect of pain modulation in trigeminal pain pathway via optogenetic activation of vlPAG excitatory neurons in rat model. This outlook could potentially assist vlPAG insight and its optogenetic approach in trigeminal neuropathic pain which aid clinicians endeavoring towards enhanced pain relief therapy in trigeminal neuralgia patients.https://doi.org/10.1186/s10194-021-01257-zMicrodialysisOptogeneticsPeriaqueductal grayThalamusTrigeminal neuralgia |
| spellingShingle | K. C. Elina Byeong Ho Oh Jaisan Islam Soochong Kim Young Seok Park Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model The Journal of Headache and Pain Microdialysis Optogenetics Periaqueductal gray Thalamus Trigeminal neuralgia |
| title | Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| title_full | Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| title_fullStr | Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| title_full_unstemmed | Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| title_short | Activation of CamKIIα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| title_sort | activation of camkiiα expressing neurons on ventrolateral periaqueductal gray improves behavioral hypersensitivity and thalamic discharge in a trigeminal neuralgia rat model |
| topic | Microdialysis Optogenetics Periaqueductal gray Thalamus Trigeminal neuralgia |
| url | https://doi.org/10.1186/s10194-021-01257-z |
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