Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury

Abstract

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation “ON” and “OFF” conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

Rich-club reorganization and related network disruptions are associated with the symptoms and severity in classic trigeminal neuralgia patients

“…Due to abundant GABAergic neurons ( Robison and Nestler, 2011 ) and the integration of dopaminergic and glutamatergic signals from pain related regions (such as the PFC and thalamus), the NAC is significantly involved in pain regulation and relief ( Harris and Peng, 2020 ). A recent animal experiment suggests that optogenetic stimulation on the NAC attenuated the hyperalgesia of TN rats, accompanied by an increased extracellular concentration of GABA, glutamate, dopamine, and acetylcholine ( Islam et al, 2021 ). Though no obvious correlation was observed between edge strength and psychological scores, which may be due to the sparsity of the SN, the aberrant links between the thalamus, NAC, and PFC may indicate an adaptive process in response to the need for emotion management in patients with chronic pain ( Tu et al, 2019 ).…”

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

“…Rats were placed into a stereotaxic apparatus while being anesthetized with a blend of zoletil and xylazine. After adjusting the skull plane to ensure that the bregma and lambda were horizontal, a small craniotomy was performed over the thalamic ventroposterior medial (VPm) area (coordinates from bregma: AP, −3.5 mm; ML, −2.8 mm) of the rat for thalamic recordings ( Islam et al, 2021 ). A quartz-insulated carbon electrode (E1011-20, Carbostar-1, Kation Scientific, Minneapolis, MN, United States) was inserted unilaterally in the VPm thalamus and slowly lowered to the depth (DV, –1.3 mm).…”

Recent update on trigeminal neuralgia

“…For the study of TN, a variety of animal models (Table 1) [3,[40][41][42][43][44][45][46][47][48][49][50][51][52][53] have been developed. All of these animal models contributed to the discovery of vital information about the TN pathway or TN therapeutic management.…”

“…The thalamus (i.e., the ventral posteromedial), limbic system, and somatosensory cortex receive the signals from these stimulated second-order neurons, which are subsequently interpreted as pain (Fig. 1) [3]. Multiple sclerosis (MS), arteriovenous malformation or saccular aneurysm, epidermoid cyst, acoustic neuroma and meningioma are some of the other reasons that can cause secondary TN.…”