Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Chronic pain poses a major social and economic burden worldwide. In Canada, it is estimated that nearly 1 in 3 individuals suffers from chronic pain, and that chronic pain costs the national economy several billion dollars per year. A type of chronic pain known as neuropathic pain is particularly challenging to treat because current pharmacotherapies are either not effective or have limited compliance due to unwanted side effects. Sympathetically maintained pain is one form of neuropathic pain that has an etiology of sympathetic nervous system involvement. Though the clinical link between sympathetic dysfunction and neuropathic pain is appreciated, our knowledge regarding the underlying anatomical and physiological mechanisms that lead to the onset and continuance of sympathetically maintained pain remain incomplete. Animal models and human studies show that peripheral nerve damage can induce abnormal coupling between sympathetic and sensory (nociceptive) neurons in the peripheral nervous system. For instance, following nerve injury, sympathetic axons undergo collateral sprouting in the affected spinal ganglia, where these new fibers can encircle the cell bodies (or somata) of sensory neurons. This aberrant sympathetic-sensory coupling causes an increased, inappropriate activation of pain signals. Given the wealth of information showing that nerve growth factor (NGF) promotes the directional growth of new sympathetic collaterals, this molecule is a likely candidate for the stimulation of sympathetic coupling onto the somata of injured sensory neurons. In this research study, we have formulated several novel hypotheses that are aimed at resolving the cellular mechanisms which elicit sympathetic-sensory coupling in sensory ganglia after nerve injury. It is our hope that new knowledge from these studies will facilitate the development of new and effective therapies that counteract sympathetically maintained pain in humans.