Therapeutic potential of 5HT2CR in alleviating spasticity and pain via modulation of motor neurons and interneurons in spinal cord injury

Numerous adverse outcomes can be resulted in limb spasm and spasticity that occur after spinal cord injury (SCI). Here, we used adeno-associated virus (AAV) vectors and Cre-driver transgenic mice to selectively overexpress 5-hydroxytryptamine2C receptor (5HT2CR) in motor, GABAergic, and Glutamatergic interneurons. Targeted overexpression in these neuronal populations attenuated spasticity-like responses and hindlimb motor deficits, and improved sensory abnormalities and affective disturbances. These behavioral improvements were associated with changes in potassium chloride cotransporter-2 (KCC2), gamma-aminobutyric acid type A receptor (GABAAR), and N-methyl-D-aspartate receptor (NMDAR) expression in spinal cord tissue, indicating that the activity of motor neurons is influenced by the expression of 5HT2CR. This work indicates that 5HT2CR represents a promising target for alleviating spasticity and neuropathic pain after SCI.