Neuropathic Pain Syndromes Associated with Nerve and Spinal Cord Injuries

While paralysis can be seen and is widely appreciated as impacting on quality-of-life after nerve and spinal cord injury, neuropathic pain also occurs in many people who have sustained these injuries. Neuropathic pain can be severe and, in many cases, does not respond to existing treatments. A major contributor is the reprogramming of injured spinal sensory neurons such that they become hyperexcitable, abnormally firing electrical impulses when they should not be. We are investigating neuropathic pain, particularly the role of sodium channels and associated molecules/mechanisms in neuropathic pain, with the goal of identifying new and more effective treatments. In addition to our studies in animal models and in vitro, we have launched a world-wide search for families that house mutations that can cause neuropathic pain. In a translational leap, we have identified gain-of-function mutations of sodium channels Nav1.7 as the cause of severe pain in inherited erythromelalgia (IEM), the "man-on-fire syndrome". We have also found upregulation of Nav1.7 in injured axon tips in neuromas from patients with neuropathic pain after nerve injury and traumatic limb amputation, a finding that has identified Nav1.7 as an important therapeutic target for human studies.

Neuropathic Pain Image

A schematic of voltage-gated sodium channel showing the locations of the known mutations in Nav1.7-related inherited pain disorders. [From Dib-Hajj et al., Trends in Neuroscience, 30(11):555-563]