Abstract
BackgroundPreceding 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.MethodsTN 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Irrespective of the numerous therapeutic approaches, trigeminal neuralgia (TN) is still deemed a valid question to treatment
Excitatory ventrolateral periaqueductal gray (vlPAG) neurons express ChR2 We observed the transfection of an associated virus (AAV) vector in our desired target “vlPAG”, which was stereotaxically identified with the Paxinos and Watson rat brain atlas in both optogenetic and null groups
Immunofluorescent images confirmed the viral expression in vlPAG in TN/ChR2 and TN/enhanced yellow fluorescent protein (EYFP) rats (Fig. 2c)
Summary
Irrespective of the numerous therapeutic approaches, trigeminal neuralgia (TN) is still deemed a valid question to treatment. The contribution of vlPAG glutamatergic neuron in itching and pain activity has been reported [8]; in addition there are experimental supports concerning its bidirectional role of excitatory and inhibitory neurons in nociception [9]. These studies are mainly focused on spinal pain modulation and less interest has been given to orofacial pain modulation. Preceding studies have reported the association of chronic neuropathic orofacial pain with altered ongoing function in the ventrolateral periaqueductal gray (vlPAG). We here reported the aspect that vlPAG neurons play in TN nociceptive processing by employing excitatory neuron-specific optogenetic approaches
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