Electronic Poster | Session 1
046 – Spinal cord injury severity modulates the development and maintenance of mechanical and thermal hypersensitivity
Courtney Bannerman (1) – Julia Segal (1) – Mitra Knezic (1) – Jaqueline Raymondi Silva (1, 2) – Caitlin Lundell-Creagh (1) – Scott Duggan (1, 2, 3) – Ian Gilron (1, 2, 3) – Nader Ghasemlou (1, 2, 3*)
Departments of Biomedical & Molecular Sciences (1) – Departments of Anesthesiology & Perioperative Medicine (2) – Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada (3)
Vast improvements have been made in recent years for the care and treatment of acute spinal cord injury (SCI), with patients living longer than ever before. However, chronic pain remains a devastating sequela of disease, severely impacting the quality of life for those living with injury. Current treatment options for SCI pain include Gabapentin and opioids, among others, with serious side effects and extensive complications associated with their use. Therefore, better understanding the mechanisms underlying this neuroimmunological response will be key to the development of new therapeutics. Current pre-clinical models of injury, such as clip-compression, hemisection, and contusion, fail to exhibit many of the signs associated with SCI pain. We therefore sought to develop a model of SCI with a strong pain phenotype using the Infinite Horizons spinal cord impactor. Moderate contusion injury, with and without compression of the cord, was carried out on female C57BL/6J mice. Mechanical and thermal sensitivity was measured using standard pain behavioural assays over 43 days. Animals with compression of the cord show significantly greater thermal heat and mechanical hypersensitivity, with reduced locomotor function, relative to mice without compression starting at day 7 after injury. Immunohistochemical analysis of spinal cord tissue revealed significantly less myelin sparing and increased macrophage activation following compression injury. Flow cytometry of the spinal cord identified at 7 days post injury there were significantly more phagocytic myeloid and microglia cells in the compression injury. We now propose the use of a contusion-compression model of SCI for the preclinical assessment of both acute and chronic pain. This model not only mimics the injury observed in humans more closely, but also better recapitulates changes in sensory function as well. This may help facilitate the translation of potential therapeutics to this underserved population.