Project 458956

Millions of Canadians suffer from chronic pain and its devastating effect on quality of life. Neuropathic pain, which is chronic pain caused by damage to the nervous system, is highly resistant to existing analgesics and often leaves patients with debilitating long-term symptoms. The discovery of new treatments is desperately needed but has proven difficult due to our incomplete understanding of pain processing. In normal pain processing, electrical signals from the skin are transmitted by specialized fibres, called primary afferents, to the brain via neurons in the spinal dorsal horn (SDH). These spinal neurons rely on chloride ions to control the transmission of sensory signals through a process called synaptic inhibition. Following peripheral nerve damage, disrupted chloride levels compromise inhibition in the SDH such that normal "touch" signals are amplified and misperceived as painful. My project will focus on identifying how chloride dysregulation impacts the SDH (its neurons and overall circuit behaviour) such that pain processing becomes dysfunctional. To do this, I will first analyze and simulate the typical electrical responses of primary afferents to touch or vibration. I will then use these simulations as input to a circuit model of the SDH to examine how touch and vibration signals from primary afferents are normally processed by spinal neurons. Finally, I will use this model to predict how chloride dysregulation alters these electrical signals such that chronic pain symptoms occur. The goal of this research project is to discover how sensory processing between primary afferents and spinal neurons is disrupted by nerve damage and how this disruption leads to chronic pain.