In addition to impairment of motor, autonomic and sensory function, severe pain is highly prevalent in patients after spinal cord injury. This project aims to better understand the cortical mechanisms and changes underlying the development of central neuropathic pain after spinal cord injury challenging the assumption that hyperexcitability of neuronal circuits can only be modified by directly blocking excitation or increasing the activity of inhibitory circuits. Our previous work has characterized the onset and maintenance of chronic central neuropathic pain in a mouse model of contusion injury. Our preliminary data also show that sensory cortical activity is initially decreased after a transient spinal cord ischemia followed by hyperactivity paralleling the onset of pain behavior. This hyperactivity and the associated pain behavior can be diminished by optogenetic stimulation of somatosensory cortex early after injury. In addition, we have shown that treadmill training can prevent the development and partially reverse pain-associated behavior in mice. We now aim to characterize in detail changes in somatosensory cortical activity after traumatic spinal cord injury in mice using patch- clamping and in vivo calcium imaging in transgenic mice. We also aim to determine whether modulating cortical activity by somatosensory training can modulate cortical hyperactivity after spinal cord injury and thereby ameliorate neuropathic pain. Thereby, we will advance our understanding of the development and maintenance of chronic pain after spinal cord injury, identify cortical mechanisms underlying the development of chronic pain that can be translated into novel pharmacological and rehabilitative treatments that interfere with homeostatic plasticity for a comprehensive pain management.
This project aims to better understand the mechanisms underlying the development of pain after spinal cord injury and how training/activity can prevent or reverse chronic pain. Thereby, findings from this research will contribute to the development of novel pharmacological and rehabilitative treatments towards comprehensive pain management.
