Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans

Objective: Although posttraumatic stress disorder (PTSD) and chronic pain frequently occur in tandem, the pathophysiological mechanisms mediating this comorbidity are poorly understood. Because excessive inflammation occurs in both conditions, we examined the cerebrospinal fluid (CSF) concentrations of inflammatory response mediators interleukin 1-beta (IL-1 beta), interleukin 6 (IL-6); interleukin 8 (IL-8), tumor necrosis factor-alpha (TNF alpha) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC). Methods: After completing baseline quantitative sensory testing (QST) and psychological profiling, all patients received an injection of capsaicin into the quadriceps muscle. Spontaneously reported pain was measured for 30 min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110 min post capsaicin injection. Inflammatory (IL-1 beta, IL-6, IL-8 TNE alpha) and anti-inflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110 min. Results: Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNF alpha, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1 beta significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10 min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70 min post injection. Conclusion: These findings show significant central nervous system (CNS) differences in the inflammatory response to a deep pain stimulus in combat veterans with and without PTSD. They support the concept that abnormally elevated neuroinflammatory response to pain stimuli may be one CNS mechanism accounting for the high co-occurrence of PTSD and pain. Published by Elsevier Ltd.