2 - (SYM 112) An in Vivo Investigation of Kappa Opioid Receptor Availability in Chronic Pain and Trauma-related Psychopathology Using [11C]EKAP PET

Introduction: Pain is often comorbid with other symptoms and clinical pictures. Altered pain processing is associated with the endogenous opioid system (EOS), and kappa opioid receptors (KOR) in particular (Leitl et al., 2010). The EOS is implicated in PTSD (Bruchas et al., 2010) and borderline personality disorder (BPD) pathophysiology (Bandelow et al. 2010; Prossin, 2010). While the exact pathway is unclear, early trauma is conceptualized to play a role in the biology of BPD (e.g., Bozzatello et al., 2021). This suggests neurobiological differences in pain experience for individuals with trauma-related psychopathology (TRP). However, these links have not been directly explored. We examined KOR and chronic pain (CP) in TRP in vivo using [11C]EKAP PET.


Methods: 18 individuals with TRP (PTSD or BPD; 50% male) were recruited from the community (CP=8, M age= 33.3 SD=9.8; no CP=10; M age=32.3, SD=8.0). Participants completed a PET scan and clinical assessment. Volume of distribution (VT: ratio of activity in tissue relative to that in blood) was computed using arterial input function. Primary analyses involved a frontolimbic circuit relevant to TRP pathophysiology. CP and pain tolerance/sensitivity were assessed by the Brief Pain Inventory and cold-pressor task, respectively. 


Results: One-way ANOVA showed significantly lower KOR availability in the frontolimbic circuit of individuals with CP relative to those without (F(1,18)=21.88, p< .001). Individuals with CP had significantly higher pain tolerance on the cold-pressor task (F(1,18)=4.61, p=.046), and KOR availability was negatively associated with pain tolerance in the full sample (r=-.49, p=.03). Lower KOR availability was correlated with average daily pain in the full sample (r=-.53, p=.014), and greater self-reported effects of pain on mood (r=-.46, p=.04), and sleep (r=-.45, p=.04). Depressive (r=-.48, p=.03) but not PTSD symptom severity was associated with lower KOR. No differences were observed in pain sensitivity or self-reported pain tolerance (p’s=.18-86), and neither was significantly related to KOR availability. Lower KOR was associated with greater frequency and intensity of childhood emotional and physical abuse and neglect (r’s=.72-.77, p’s=.02-.04) in those with CP only. 


Discussion: Findings demonstrated lower KOR availability in those with TRP who experience CP, and highlighted the potential role of early trauma in these relationships. Larger studies are warranted. However, KOR may be a transdiagnostic treatment target for TRP, especially among those with CP.