Unraveling the PVTGlu-mPFCGlu circuit: A new frontier in chronic pain management for bone cancer pain

Bone cancer pain (BCP) is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone metastasis. BCP impairs patients' quality of life. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms BCP patients. Central nervous system sensitization performs a crucial role in pain-regulating perception in BCP. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Prelimbic cortex (mPFC) and paraventricular thalamus (PVT) in BCP mice. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVT and mPFC. Inhibition of the input from PVT glutamatergic neurons to mPFC glutamatergic neurons alleviates chronic pain in BCP, whereas activation of the PVT^Glu-mPFC^Glu projection induces chronic pain in mice. These findings imply a pivotal role for the PVT^Glu-mPFC^Glu circuit in the regulation of chronic pain in BCP.