Background & Aims
Posttraumatic stress symptoms (PTSS) are commonly experienced by people suffering from chronic pain disorders. Reduced grey matter volume in stress-sensitive brain regions, including the striatum, the hippocampus, the amygdala, the anterior and middle cingulate cortices, the medial prefrontal cortex, and the insula has been reported in independent studies of people with chronic pain and in people reporting higher levels of PTSS (e.g. 1). However, the relationship between chronic pain, PTSS and grey matter volume among these stress-sensitive regions remains unclear. This study aims to determine whether the severity of PTSS moderates the differences in brain morphology between people with chronic pain and healthy (pain-free) controls. We hypothesised that the severity of PTSS will be associated with smaller grey matter volume of these regions, and that cumulative effects of chronic pain and PTSS severity would be evident in these regions relative to healthy controls.
Methods
Fifty-two people with chronic pain (including temporomandibular disorder (n=15), trigeminal neuropathic pain (n=14), burning mouth (n=1), trigeminal neuralgia (n=6), and spinal cord injury (n=16)) and 38 pain-free healthy controls (HC) underwent T1-weighted magnetic resonance imaging (MRI) scan. Severity of PTSS was measured using the civilian version of the PTSD-checklist (PCL-C) (2). A series of multiple linear regressions determined the main effects of group, PTSS severity (PCL-C total score) and their interaction on grey matter volume of targeted regions (hippocampus, amygdala, nucleus accumbens, putamen caudate nucleus, pallidum, thalamus, medial prefrontal cortex, anterior and posterior insula, anterior and middle cingulate gyri and middle frontal gyrus), accounting for age, sex and total intracranial volume. Moderation analyses were performed in case of significant association between the interaction term and brain morphology.
Results
The interaction term was significantly associated with variations in grey matter volume in the left and right putamen, the left middle cingulate gyrus and the right posterior insula. The first set of moderation analyses using PTSS severity as moderator of the group differences on brain morphology, indicated that compared to HCs, people with Chronic pain showed significantly smaller left and right putamen only when reporting higher (not at lower/average) PTSS levels, and significantly larger left middle cingulate gyrus and right posterior insula at lower PTSS levels only (not at average/high levels). The second set of moderation analyses using group as the moderator of the relationship between PTSS severity and brain morphology, showed that increasing PTSS severity was significantly associated with larger left and right putamen only in HCs, and significantly associated with smaller left middle cingulate gyrus and right posterior insula, only in people with Chronic Pain.
Conclusions
The severity of PTSS reported was a significant moderator of the grey matter alterations observed in people with chronic pain. In particular, higher levels of PTSS were associated with larger putamen and right posterior insula in pain-free participants only, potentially reflecting mechanisms of resilience to trauma in this group. In addition, higher levels of PTSS were associated with smaller left middle cingulate gyrus, a core region of the so-called “pain matrix” and default-mode network has strong links with the somatosensory network and is critical for empathy, especially toward pain-related stimuli. This is largely consistent with impacts of trauma on similar brain regions across various psychiatric conditions including PTSD, depression, or schizophrenia. Replication in larger sample is necessary, especially to confirm that the observed effects are common to different chronic pain conditions as suggested here.
References
(1) Abdallah CG and Geha P (2017) Chronic Pain and Chronic Stress: Two Sides of the Same Coin? Chronic Stress (Thousand Oaks) 1
(2) Weathers F, Litz B, Herman D, Huska J and Keane T (October 1993) The PTSD Checklist (PCL): Reliability, Validity, and Diagnostic Utility. Paper presented at the Annual Convention of the International Society for Traumatic Stress Studies, San Antonio, TX.