Previous studies documented that stimulation of the motor cortex and periaqueductal gray (PAG) was effective management for refractory neuropathic pain, however, our understanding about the neuroanatomical and neurochemical mechanisms of motor cortex and PAG stimulation is still limited. We used a modified retrograde multisynaptic pseudorabies virus tracer PRV-614 injection to the kidney with an attempt to provide morphological evidence of the neuroanatomical circuit among motor cortex, PAG, rostral ventromedial medulla (RVM), and kidney. The principal findings of this study are: (1) Spinal nerve injury induced an increase of c-Fos/MC4R-GFP dual labeled neurons in motor cortex. (2) The inoculation of PRV-614 into the kidney resulted in retrograde infection of neurons in RVM, PAG and motor cortex, and PRV-614/MC4R-GFP dual labeled neurons were detected in RVM, PAG and motor cortex. (3) MC4R-GFP/MOR dual labeled neurons were detected in PAG, and 50%-70% of the GFP-positive neurons in the ventrolateral PAG were MOR-immunoreactive. These results together demonstrate that MC4R signaling in motor cortex-PAG-RVM neural circuit may participate in the descending modulation of nociceptive transmission. The data provided by this study suggest that melanocortinergic-sympathetic signaling of motor cortex-PAG-RVM neural circuit may be a potential target for the inhibition of nociceptive transmission.