Optogenetic stimulation of the motor cortex alleviates neuropathic pain in rats of infraorbital nerve injury with/without CGRP knock-down

Abstract

Background: Previous studies have reported that electrical stimulation of the motor cortex is effective in reducing trigeminal neuropathic pain; however, the effects of optical motor cortex stimulation remain unclear. Objective: The present study aimed to investigate whether optical stimulation of the primary motor cortex can modulate chronic neuropathic pain in rats with infraorbital nerve constriction injury. Methods: Animals were randomly divided into a trigeminal neuralgia group, a sham group, and a control group. Trigeminal neuropathic pain was generated via constriction of the infraorbital nerve and animals were treated via selective inhibition of calcitonin gene-related peptide in the trigeminal ganglion. We assessed alterations in behavioral responses in the pre-stimulation, stimulation, and post-stimulation conditions. In vivo extracellular recordings were obtained from the ventral posteromedial nucleus of the thalamus, and viral and α-CGRP expression were investigated in the primary motor cortex and trigeminal ganglion, respectively. Results: We found that optogenetic stimulation significantly improved pain behaviors in the trigeminal neuralgia animals and it provided more significant improvement with inhibited α-CGRP state than active α-CGRP state. Electrophysiological recordings revealed decreases in abnormal thalamic firing during the stimulation-on condition. Conclusion: Our findings suggest that optical motor cortex stimulation can alleviate pain behaviors in a rat model of trigeminal neuropathic pain. Transmission of trigeminal pain signals can be modulated via knock-down of α-CGRP and optical motor cortex stimulation.

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

“…These sensory nerve fibers are mainly Aδ-and C-fibers, and their cell bodies are rooted in the trigeminal ganglion (TG). Nociceptive signals are conveyed through these trigeminal afferents and projected to the trigeminal spinal caudalis (Vc) nucleus of the brainstem, where they synapse with the second-order neurons and are projected to the somatosensory and limbic cortices via reciprocal aberrant sensory signals assembled in the sensory area of the thalamus (i.e., the VPM), thereby initiating pain sensation and behavioral changes [2,[17][18][19][20][21]. Similar findings were observed in our study, with TN animals exhibiting painful behavioral responses in all behavior tests.…”

“…The spinal trigeminal nucleus conveys craniofacial somatosensory information to the thalamus from the brainstem. Earlier studies also showed that TN is associated with anatomical and biochemical changes in the VPM thalamus that cause thalamic tonic firing hyperresponsiveness and an increase in the burst firing rate [1,2,[53][54][55]. Since stimulation of the NAcc causes alteration in its robust interconnections with areas involved in pain circuitry, manipulation of these networks produces antinociception with downstream effects.…”

“…To generate the TN model, CCI-ION surgery was performed in 32 animals as previously described [2,64] (Figure S2). Briefly, after achieving general anesthesia, the animals were mounted onto the surgical field in a prone position.…”

“…Trigeminal neuralgia (TN) or "tic douloureux" can present as an extreme form of chronic neuropathic pain and include a spontaneous and exaggerated painful response alongside a negative affective, motivational, and cognitive state [1,2]. Chronic constriction injury of the infraorbital nerve (CCI-ION) is an established model for TN experiments, as this model exhibits the principal TN syndromes.…”

“…Chronic constriction injury of the infraorbital nerve (CCI-ION) is an established model for TN experiments, as this model exhibits the principal TN syndromes. Although the typical form of TN responds satisfactorily to surgical interventions, the atypical form of TN does not [2,3]. To overcome this and find an efficacious solution, maladaptive neural circuits linked with different states in the brain have been widely studied.…”