Unraveling the PVNGlu-PrLGlu circuit: A new frontier in chronic pain management for lumbar disc herniation.

Lumbar disc herniation (LDH) refers to a pathological state in which the nucleus pulposus (NP) protrudes, leading to compression or irritation of nerve roots. This condition manifests with clinical symptoms including lower back and leg pain, hyperalgesia, and altered sensory perceptions. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms LDH patients. The central nervous system sensitization performs a crucial role in pain-regulating perception in LDH. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Paraventricular nucleus of the hypothalamus (PVN) and Prelimbic cortex (PrL) in LDH rats. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVN and PrL. Inhibition of the input from PVN glutamatergic neurons to PrL glutamatergic neurons alleviates chronic pain in LDH, whereas activation of the PVN^Glu-PrL^Glu projection induces chronic pain in rats. These findings imply a pivotal role for the PVN^Glu-PrL^Glu circuit in the regulation of chronic pain in LDH.