Re‐exposure to a Traumatic Event Amplifies the Duration and Severity of Co‐morbid Chronic Pain in an Animal Model of Post‐traumatic Stress Disorder
Authors: Schalo Ian C , Simpson‐Durand Cindy , Dib Patrick , Zhang Yong , Standifer Kelly M. 
Published: November 2023

Post‐traumatic stress disorder (PTSD) is a debilitating condition affecting up to 35% of combat veterans and between 7–8% of the general populace. Heightened anxiety/hyperarousal and chronic pain commonly co‐occur in both civilian and veteran PTSD populations. The shared co‐morbidity of PTSD with chronic pain negatively impacts the treatment of both disorders. Single‐prolonged stress (SPS) is an established animal model of PTSD capable of facilitating development of symptoms similar to those observed in human patients, including decreased pain threshold and amplified anxiety and fear responses. We have reported that SPS produces tactile allodynia that persists for over 5 weeks following the initial stress exposure. Many PTSD patients have experienced multiple traumatic events, and/or re‐experience the stress following exposure to reminders (cues) of that traumatic event. Because the severity of PTSD in humans correlates with the severity of the trauma, we felt it important to explore how re‐exposure to one of the original stressors altered the severity of existing co‐morbid nociceptive hypersensitivity. Therefore we have introduced a latent re‐stress component to the established SPS model in order to better understand how re‐exposure to a traumatic event may alter the duration and intensity of PTSD and co‐morbid symptoms and their molecular underpinnings.

Male Sprague‐Dawley rats were subjected to single prolonged stress (SPS) at day 0. At day 21, half of the SPS rats were re‐stressed with 2 hour restraint, one of the original SPS stressors. The development of PTSD and co‐morbid symptoms was monitored over the course of 60 days by weekly nociception assessment using the von Frey assay for mechanical nociceptive sensitivity and Hargreaves’ assay for thermal nociceptive sensitivity. Anxiety was assessed by elevated plus maze at days 9, 30, and 51 of the initial SPS and days 9 and 21 of the re‐stressed group. Results from nociceptive testing indicate a prolonged and significant decrease in pain threshold of rats subjected to SPS + re‐stress as compared to SPS alone. Preliminary studies indicate that anxiety symptoms persisted for up to 52 days.

Our results indicate that exposure to a re‐stress event following SPS increased the severity and duration of nociceptive hypersensitivity and anxiety in an animal model of PTSD. These findings suggest that the molecular markers that changed with SPS alone also will be found to exhibit exacerbated intensity and/or duration of effect following re‐stress. Future studies will examine those molecular changes following re‐stress with the goal of improving treatment and preventing continued deterioration following PTSD.

These studies were approved by the OUHSC IACUC committee and conformed to the FASEB Statement of Principles for the use of animals in research and education.

Support or Funding Information

University of Oklahoma Health Sciences Center Vice President for Research and the Presbyterian Health Foundation Bridge Grant Program