Glutamatergic Projection from the Ventrolateral Periaqueductal Gray to the Parafascicular Nucleus of the Thalamus Contributes to the Modulation of Neuropathic Pain in Mice.

Chronic pain is frequently accompanied by increased pain sensitivity and affective disturbances. The ventrolateral periaqueductal gray (vlPAG) and the parafascicular nucleus of the thalamus (PF) are key nodes in pain modulation. However, the functional role of the vlPAG-PF neural pathway remains poorly understood. In this study, we employed an integrative approach combining neuroanatomical tracing and chemogenetic techniques to investigate the role of the vlPAGvGluT2-PF neural pathway in pain modulation. Our results demonstrate that vGluT2-positive neurons in the vlPAG project to the PF. Chemogenetic inhibition of the vlPAGvGluT2-PF pathway increased mechanical sensitivity in naïve mice, whereas activation of this pathway alleviated mechanical hypersensitivity in mice subjected to spared nerve injury (SNI). These results demonstrate that the vlPAGvGluT2-PF pathway is involved in the modulation of neuropathic pain and provide experimental evidence for further investigation of this pathway.