Pain modulation effect on motor cortex after optogenetic stimulation in shPKCγ knockdown dorsal root ganglion-compressed Sprague-Dawley rat model

Abstract

Neuropathic pain can be generated by chronic compression of dorsal root ganglion (CCD). Stimulation of primary motor cortex can disrupt the nociceptive sensory signal at dorsal root ganglion level and reduce pain behaviors. But the mechanism behind it is still implicit. Protein kinase C gamma is known as an essential enzyme for the development of neuropathic pain, and specific inhibitor of protein kinase C gamma can disrupt the sensory signal and reduce pain behaviors. Optogenetic stimulation has been emerged as a new and promising conducive method for refractory neuropathic pain. The aim of this study was to provide evidence whether optical stimulation of primary motor cortex can modulate chronic neuropathic pain in CCD rat model. Animals were randomly divided into CCD group, sham group, and control group. Dorsal root ganglion-compressed neuropathic pain model was established in animals, and knocking down of protein kinase C gamma was also accomplished. Pain behavioral scores were significantly improved in the short hairpin Protein Kinase C gamma knockdown CCD animals during optic stimulation. Ventral posterolateral thalamic firing inhibition was also observed during light stimulation on motor cortex in CCD animal. We assessed alteration of pain behaviors in pre-light off, stimulation-light on, and post-light off state. In vivo extracellular recording of the ventral posterolateral thalamus, viral expression in the primary motor cortex, and protein kinase C gamma expression in dorsal root ganglion were investigated. So, optical cortico-thalamic inhibition by motor cortex stimulation can improve neuropathic pain behaviors in CCD animal, and knocking down of protein kinase C gamma plays a conducive role in the process. This study provides feasibility for in vivo optogenetic stimulation on primary motor cortex of dorsal root ganglion-initiated neuropathic pain.

Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington’s disease

“…In the case of HD, the severe loss of GABAergic medium spiny neurons in the striatum was targeted as the first character of the HD brain and the degeneration starts in the caudate and putamen. And due to this striatal tissue death, the natural motor activity of an entity face hindrances as the important role of the striatum in controlling the movement of the opposite side of the body is irrefutable [41][42][43]. Behavior results of this study also exhibited the same phenomenon with significant motor activity deficits in the left forelimb after injecting the Htt virus in the right striatum.…”

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

“…We used a laser power supply with a wavelength of 473 nm (BL473T3-100, ADR-700D, Shanghai, China) and a waveform generator (Keysight 33511b-CFG001, Keysight, Santa Rosa, CA, USA) to regulate the waveform and pulse width of the laser. The laser's intensity was set to 10 mW, the pulse width was set to 4 ms, and the pulses were set to 20 Hz [2,14,69]. A blue light was delivered via the optical fiber through a rotary joint patch cable that enables movement during testing.…”

“…Activity in the thalamic neurons was divided into burst rates (bursts/s) and overall firing rates (spikes/s) in each optical stimulation condition using NeuroExplorer software (Neuralynx Inc. Bozeman, MT, USA) [2,14]. The activity was assessed for 5 min in each state: pre-stimulation, stimulation, and post-stimulation.…”

“…The NAcc integrates the mesencephalic dopaminergic signals from the VTA and SN, as well as glutamatergic information from the PFC, amygdala, thalamus, prelimbic cortex, hippocampus, and subiculum [5,9]. Therefore, to analyze the effects of stimulating NAcc in a TN condition, we used an optogenetic stimulation approach with the human synapsin promoter to increase the activity of GABAergic neurons in NAcc, as it is well-established that pptogenetics is suitable for understanding the functional dissection of neural circuits that manipulate the neural substrates of behavior, as it can achieve more precise temporal and spatial control over specific neural populations than pharmacological or electrical interventions [7,13,14].…”

The role of the anterior pretectal nucleus in pain modulation: A comprehensive review

“…These techniques reveal a network of encephalic regions involved in chronic pain modulation. Common to both acute and chronic pain is the dynamic process involving reciprocal communication between the cortex and thalamus (Alitto & Usrey, 2003; Crandall et al., 2015; Islam et al., 2020; Youssef et al., 2019). The cortex has a strong influence on thalamic activity; therefore, corticothalamic feedback contributes to thalamic plasticity in response to changes in afferent activity (Groh et al., 2018).…”