Photogenetics Inhibits the Activity of Glutamate Neurons Projected from the Motor Cortex to the Ventroposterolateral Nucleus of the Thalamus to Alleviates Central Post-Stroke Pain in Rats

The "central sensitization" and "central imbalance" theories suggest that central post-stroke pain (CPSP) is the result of neuronal overactivity and an imbalance between excitatory and inhibitory functions of the nervous system caused by damage to the sensory system. The ventral posterior lateral nucleus of the thalamus (VPL) and the primary motor cortex (M1) are key brain regions for nociceptive message transmission. However, the effects of inhibiting M1-VPL glutamatergic projections in CPSP remain unclear. his study investigates the efficacy of photogenetic inhibition of M1-VPL glutamatergic neuron excitability in a rat model of CPSP. CPSP rats underwent M1 injection with rAAV encoding an inhibitory photosensitive protein, followed by implantation of an optical fiber sleeve above the VPL and subsequent 10 W, 20 Hz, 5 ms yellow laser (589 nm) irradiation. The irradiation scheme was to start from the 3rd day after the CPSP mode, light for 2 min, turn off for 3 min, and repeat 6 times a day for 12 consecutive days. We observed that the mechanical and thermal pain thresholds were increased in CPSP rats, and the expressions of M1 pain-related factors c-Fos, vesicular glutamate transporter protein 2 (VGLUT2), and N-methyl-D-aspartate receptor subtype 2B (NR2B) were down-regulated. These findings indicate that photogenetic inhibition of M1-VPL glutamatergic projection can relieve pathologic pain in CPSP rats.