Title: Long Duration, Low-Concentration Topical Capsaicin Diminishes Central Sensitization
Thesis Supervisor: Dr. John Kramer
Committee Members: Dr. Jean-Sébastien Blouin, Dr. Brian Cairns
Chair: Dr. Cornelia Laule
Abstract: The development of chronic pain is typically predicated by neuroplastic changes within the spinal cord in response to persistent noxious stimuli, termed central sensitization. Sensitization increases the sensitivity to stimuli of neurons directly in contact with the initial noxious stimulus, termed primary hyperalgesia, as well as those in the adjacent regions, termed secondary hyperalgesia. TRPV1 receptors, found throughout the spinal cord and periphery, are key contributors to the development of sensitization. Capsaicin, the active ingredient in chili peppers, is a known agonist of TRPV1 receptors and, due to the unique ability of these receptors to become defunctionalized with intense or prolonged capsaicin exposure, is a common ingredient in pain relieving ointments. Defunctionalization, via capsaicin, eliminates the typical primary sensitization and has been demonstrated through the application of high dosage (>5%) capsaicin treatments. The purpose of this study was to analyze the effects of defunctionalizing capsaicin-sensitive nociceptors, using a prolonged low concentration (<1%) capsaicin treatment, on peripheral and central pain development. Following the application period, a battery of quantitative sensory assessments were performed. Following our intervention, heat and cold pain perceptions during heat and cold evoked potentials were significantly lower in the capsaicin region compared to the control region. Analysis of the neurophysiological outcomes from the evoked potentials, revealed that CHEP but not CEP amplitudes at the capsaicin treatment region were significantly decreased. Heat pain and warm detection thresholds were significantly increased in the capsaicin treated region whereas cold pain or cold detection thresholds did not change. Mechanical pain sensitivity following the heat sensitization protocol, increased in the control but not the capsaicin region. These findings indicate that prolonged, low-concentration, capsaicin application successfully desensitized TRPV1 receptors and diminished secondary hyperalgesia development in the capsaicin treated region. These findings suggest that the use of low concentration capsaicin may be beneficial in preventing central sensitization in conditions such as chronic pain.