title: Posttraumatic stress disorder influences the nociceptive and intrathecal cytokine response to a painful stimulus in combat veterans.
abstract: 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-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor-alpha (TNFα) and interleukin 10 (IL-10) after prolonged suprathreshold pain stimulus in 21 male combat veterans; 10 with PTSD and 11 combat controls (CC).
  
  
  
  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 30min after the capsaicin injection. The evoked pain measure of temporal summation was tested between 70 and 110min post capsaicin injection. Inflammatory (IL-1β, IL-6, IL-8 TNFα) and anti-inflammatory (IL-10) CSF cytokines were measured before (baseline) and after capsaicin injection over a time frame of 110min.
  
  
  
  Following intramuscular capsaicin injection, pro-inflammatory cytokines [TNFα, IL-6, IL-8] significantly increased (percent rise from baseline) in both groups, whereas IL-1β significantly increased in the PTSD group only. The anti-inflammatory cytokine IL-10 showed an immediate (within 10min) increase in the CC group; however, the IL-10 increase in the PTSD group was delayed and not consistently elevated until 70min post injection.
  
  
  
  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.
authors.affiliation: VA Center of Excellence for Stress and Mental Health, San Diego, CA, United States; University of California San Diego, San Diego, CA, United States; VA San Diego Healthcare System, San Diego, CA, United States; Clinical and Translational Research Institute, San Diego, CA, United States. Electronic address: ilerman@ucsd.edu.
authors.forename: Imanuel
authors.initials: I
authors.lastname: Lerman
authors.affiliation: University of California San Diego, San Diego, CA, United States.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Davis
authors.affiliation: Desert Clinic Pain Institute, Palm Springs, CA, United States.
authors.forename: Tobias Moeller
authors.initials: TM
authors.lastname: Bertram
authors.affiliation: University of California San Diego, San Diego, CA, United States; Clinical and Translational Research Institute, San Diego, CA, United States.
authors.forename: James
authors.initials: J
authors.lastname: Proudfoot
authors.affiliation: VA Center of Excellence for Stress and Mental Health, San Diego, CA, United States; University of California San Diego, San Diego, CA, United States; VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hauger
authors.affiliation: Psychology, University of Wisconsin, Madison, WI, United States.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Coe
authors.affiliation: University of California San Diego, San Diego, CA, United States; VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Piyush M
authors.initials: PM
authors.lastname: Patel
authors.affiliation: VA Center of Excellence for Stress and Mental Health, San Diego, CA, United States; University of California San Diego, San Diego, CA, United States; VA San Diego Healthcare System, San Diego, CA, United States.
authors.forename: Dewleen G
authors.initials: DG
authors.lastname: Baker
mesh_terms: D000328:Adult; D055826:Afghan Campaign 2001-; D003130:Combat Disorders / Q000134:cerebrospinal fluid*; D006801:Humans; D015850:Interleukin-6 / Q000134:cerebrospinal fluid*; D016209:Interleukin-8 / Q000134:cerebrospinal fluid*; D054542:Iraq War, 2003-2011; D008297:Male; D059226:Nociceptive Pain / Q000134:cerebrospinal fluid*; D013313:Stress Disorders, Post-Traumatic / Q000134:cerebrospinal fluid*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*; D014728:Veterans; D055815:Young Adult
chemical_list: C508606:CXCL8 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Cerebrospinal fluid; Chronic pain; Cytokine; Neuroinflammation; Pain; Posttraumatic stress disorder