Pain Relief in a Trigeminal Neuralgia Model via Optogenetic Inhibition on Trigeminal Ganglion Itself With Flexible Optic Fiber Cannula

Abstract

The trigeminal ganglion (TG) is the primary site of aberration in trigeminal neuralgia (TN), and hence a crucial site where afferent input can be modulated. Here, we postulated that inhibiting TG via optogenetics using flexible optic cannula would diminish brainstem trigeminal nucleus caudalis (TNC) neuronal activity and pain behavior in TN rat model. Infraorbital nerve constriction was employed to induce TN in female Sprague-Dawley rats, while naive and sham rats served as controls. TG-directed microinjections of AAV virus containing either the optogenetic or null vector were delivered to rats in each group. In vivo electrophysiological responses were obtained from the ventral posteromedial nucleus (VPm) of the thalamus with simultaneous TG optogenetic stimulation using flexible optic cannula as well the effects on behavioral responses were investigated. Recordings in TN rats revealed a decrease in burst firing activity during yellow laser driven inhibition on TG, as well as considerably improved behavioral responses. In contrast, we noticed persistent hypersensitivity and increased tonic firing with blue laser stimulation which indicates that TG inhibition can synchronize trigeminal pain signal transmission in a TN animal model. The potential of an optogenetic approach in TG itself with flexible optic fiber to directly disrupt the trigeminal pain circuitry delivers fundamental underpinnings toward its prospective as a trigeminal neuralgia management.

Trigeminal ganglion itself can be a viable target to manage trigeminal neuralgia

“…We followed the stereotaxic technique to inject the optogenetic virus into TG as mentioned in earlier studies [ 51 , 52 ]. In addition, we employed flexible optic fiber to modulate the TG activity upon stimulation, which ensures high-quality coupling and durability [ 38 ]. Specific targeting and understanding of the molecular perspectives in trigeminal ganglion may help highlight the potential therapeutic intervention in orofacial neuropathic pain.…”

“…We have demonstrated that thalamic relay nuclei and the trigeminal brainstem, which direct to the somatosensory cortex, are modified by halorhodopsin-mediated inhibition of TG. Additionally, we highlighted that the inhibition has a significant impact on bursting activity and that thehyperpolarization results in a general reduction in thalamic discharge [ 38 ].…”

GFAP-NpHR mediated optogenetic inhibition of trigeminal nucleus caudalis attenuates hypersensitive behaviors and thalamic discharge attributed to infraorbital nerve constriction injury

“…Following ION constriction or sham surgery, anesthetized rats were mounted on a stereotaxic platform for virus injection into our designated brainstem region (TNC). The rat's body temperature was maintained at 36 °C with the aid of a heating pad, and each group received the appropriate viral injection following the previous protocol [ 23 , 24 ]. The coordinates were defined as mediolateral (ML) from the midline, anterior–posterior (AP) from the bregma, and dorsoventral (DV) from the brain's pial surface.…”