The potential role of chronic pain and the polytrauma clinical triad in predicting prodromal PD: A cross-sectional study of U.S. Veterans

Abstract

Introduction: The research criteria for prodromal Parkinson disease (pPD) depends on prospectively validated clinical inputs with large effect sizes and/or high prevalence. Neither traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), nor chronic pain are currently included in the calculator, despite recent evidence of association with pPD. These conditions are widely prevalent, co-occurring, and already known to confer risk of REM behavior disorder (RBD) and PD. Few studies have examined PD risk in the context of TBI and PTSD; none have examined chronic pain. This study aimed to measure the risk of pPD caused by TBI, PTSD, and chronic pain.

Methods: 216 US Veterans were enrolled who had self-reported recurrent or persistent pain for at least three months. Of these, 44 met criteria for PTSD, 39 for TBI, and 41 for all three conditions. Several pain, sleep, affective, and trauma questionnaires were administered. Participants' history of RBD was determined via self-report, with a subset undergoing confirmatory video polysomnography.

Results: A greater proportion of Veterans with chronic pain met criteria for RBD (36 % vs. 10 %) and pPD (18.0 % vs. 8.3 %) compared to controls. Proportions were increased in RBD (70 %) and pPD (27 %) when chronic pain co-occurred with TBI and PTSD. Partial effects were seen with just TBI or PTSD alone. When analyzed as continuous variables, polytrauma symptom severity correlated with pPD probability (r = 0.28, P = 0.03).

Conclusion: These data demonstrate the potential utility of chronic pain, TBI, and PTSD in the prediction of pPD, and the importance of trauma-related factors in the pathogenesis of PD.

Keywords: Chronic pain; Neurotrauma; Parkinson disease; Prodromal; REM sleep Behavior Disorder.

Fig. 1

Association between trauma factors with prodromal Parkinson Disease (pPD). A) Proportion of participants screening positive for REM Sleep Behavior Disorder (RBD) on the RBD1Q (chi square, p < 0.0001). B) Proportion of participants with polysomnography-confirmed RBD (P = 0.04). C) Proportion of participants defined as probable pPD based on the prodromal calculator (P = 0.03). D) Mean pPD probability percentage plotted for each group. Mean probability indicated by thick line: 8.4 %, 18.1 %, 23.7 %, and 27.1 % for the Control, CP, CP + 1, and PCT groups, respectively. Thick gray lines indicate 25 %-75 % interquartile range. E) Composite score of PCT severity (comprised of NIH PROMIS pain intensity and pain interference, PCL-5, and NSI; normalized to 0–100 %) plotted against probability percentage of pPD (P = 0.03; r = 0.28; n = 159). CP = chronic pain; CP + 1 = chronic pain + either TBI or PTSD. PCT = polytrauma clinical triad (chronic pain + TBI + PTSD); NIH PROMIS-PI = National Institutes of Health Patient-Reported Outcomes Measurement Information System; PCL-5 = Post-traumatic stress disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; NSI = Neurobehavioral Symptom Inventory. * P < 0.05; **** P < 0.0001.