Brain Connectivity Predicts Chronic Pain in Acute Mild Traumatic Brain Injury.

OBJECTIVES: Previous studies have established the role of the cortico-mesolimbic and descending pain modulation systems in chronic pain prediction. Mild traumatic brain injury (mTBI) is an acute pain model where chronic pain is prevalent and complicated for prediction. In this study, we set out to study whether functional connectivity (FC) of the nucleus accumbens (NAc) and the periaqueductal gray matter (PAG) is predictive of pain chronification in early-acute mTBI. METHODS: To estimate FC, resting-state functional magnetic resonance imaging (fMRI) of 105 participants with mTBI following a motor vehicle collision was acquired within 72 hours post-accident. Participants were classified according to pain ratings provided at 12-months post-collision into chronic pain (head/neck pain ≥30/100, n = 44) and recovery (n = 61) groups, and their FC maps were compared. RESULTS: The chronic pain group exhibited reduced negative FC between NAc and a region within the primary motor cortex corresponding with the expected representation of the area of injury. A complementary pattern was also demonstrated between PAG and the primary somatosensory cortex. PAG and NAc also shared increased FC to the rostral anterior cingulate cortex (rACC) within the recovery group. Brain connectivity further shows high classification accuracy (area under the curve [AUC] = .86) for future chronic pain, when combined with an acute pain intensity report. INTERPRETATION: FC features obtained shortly after mTBI predict its transition to long-term chronic pain, and may reflect an underlying interaction of injury-related primary sensorimotor cortical areas with the mesolimbic and pain modulation systems. Our findings indicate a potential predictive biomarker and highlight targets for future early preventive interventions. ANN NEUROL 2022;92:819-833.

Head- and neck-related symptoms post-motor vehicle collision (MVC): Separate entities or two-sides of the same coin?

BACKGROUND AND AIM: Although post-motor vehicle collision (MVC) pain and symptoms are largely convergent among those with mild traumatic brain injury (mTBI) and whiplash associated disorder (WAD), and patients oftentimes report initial neck and head complaints, the clinical picture of mTBI and WAD has been primarily studied as separate conditions which may result in an incomplete clinical picture. As such, this study was conducted to explore the role of pain and post-traumatic psychological features in explaining both head and neck-related symptom variability in a cohort of post-collision patients. This is with the goal of disentangling if contributory factors are uniquely related to each diagnosis, or are shared between the two. METHODS: Patients recruited in the very early acute phase (<72 h) returned for clinical and psychological assessment at 6 months post-accident. In order to determine which factors were unique and which ones were overlapping the same potential contributors: mean head pain, mean neck pain, female gender, number of post-collision painful body areas, PTSD, and depression were included in the regression models for both neck disability index (NDI) and Rivermead post-concussion symptoms questionnaire (RPQ). RESULTS: Of 223 recruited participants, 70 returned for a follow-up visit (age range 18-64, mean(SD) 37.6 (11.9), 29F). This cohort primarily met the criteria for mTBI, but also fulfilled the criteria for whiplash, reinforcing the duality of injury presentation. Correlations existed between the NDI and RPQ scores (Spearman's ρ=0.66, p<0.001), however overlap was only partial. Regression analysis showed that after the removal of area-of-injury pain neck related disability (r = 0.80, p <0.001) was explained solely by number of painful body areas (ß=0.52, p <0.001). In contrast, post-concussion syndrome symptoms (r = 0.86, p<0.001) are influenced by clinical pain, painful body areas (ß=0.31, p = 0.0026), female gender (ß=0.19, p = 0.0053), and psychological factors of depression (ß=0.31, p = 0.0028) and PTSD symptoms (ß=0.36, p = 0.0013). CONCLUSIONS: It seems that while mechanisms of neck- and head-related symptoms in post-collision patients do share a common explanatory feature, of residual body pain, they are not entirely overlapping. In that psychological factors influence post-concussion syndrome symptoms, but not post-whiplash neck disability.

Explaining very early acute mild traumatic brain injury after motor vehicle collision pain variability: additive value of pain sensitivity questionnaire.

INTRODUCTION AND OBJECTIVES: Chronic pain is a common postcollision consequence. Wherein, a clearer understanding of acute pain can help stem the acute-to-chronic pain transition. However, the variability of acute pain is only partially explained by psychophysical pain characteristics as measured by quantitative sensory testing. The Pain Sensitivity Questionnaire (PSQ) may reflect inherent psychocognitive representations of patient's sensitivity and thus may reveal less-explored pain dimensions. In the vein of the biopsychosocial approach, this study aimed to explore whether PSQ holds additive value in explaining head and neck pain reports in very early acute-stage mild traumatic brain injury (mTBI) after collision, above the use of psychophysical assessment. METHODS: Study cohort (n = 130) consisted of mTBI patients (age range 19-66, 57 F) after accident with area-of-injury pain of at least 20 on the day of testing (mean pain 58.4 ± 21.6, range 20-100 Numerical Pain Scale) who underwent clinical, psychophysical, and pain-related psychological assessment within 72-hour after injury. RESULTS: Pain Sensitivity Questionnaire scores were significantly correlated with acute clinical, psychophysical, and pain-related psychological measures. Regression model (R 2 = 0.241, P < 0.001) showed that, together, age, sex, high PSQ, enhanced temporal summation, and less-efficient conditioned pain modulation explained head and neck pain variance. This model demonstrated that the strongest contribution to degree of postinjury pain was independently explained by PSQ (ß = 0.32) and then pressure pain threshold-conditioned pain modulation (ß = -0.25). CONCLUSION: Appraisal of cognitive daily-pain representations, by way of memory and imagination, provides an additional important dispositional facet to explain the variability in the acute mTBI postcollision clinical pain experience, above assessing nociceptive responsiveness to experimentally induced pain.

Psychophysic-psychological dichotomy in very early acute mTBI pain: A prospective study.

OBJECTIVE: To characterize the pain-related somatosensory and psychological presentation of very early acute patients with a mild traumatic brain injury (mTBI). METHODS: Patients with an mTBI participated in a prospective observational study undergoing clinical, psychophysic, and psychological assessment within 72 hours after the accident. Healthy controls underwent similar protocol. RESULTS: One hundred acute patients with an mTBI (age 36 ± 12.5 [SD] years, range 19-67 years, 42 women) and 80 healthy controls (age 43 ± 14.3 years, range 24-74 years, 40 women) participated. Patients with an mTBI demonstrated a pronociceptive psychophysic response in most tests such as less efficient pressure-pain threshold-conditioned pain modulation (0.19 ±0.19±.09 vs. 0.91±.10 kg, p < 0.001) and lower temperature needed to elicit a Pain50 response (44.72 ± 0.26°C vs 46.41 ± 0.30°C, p < 0.001). Their psychophysic findings correlated with clinical pain measures, e.g., Pain50 temperature and mean head (r = -0.21, p = 0.045) and neck (r = -0.26, p = 0.011) pain. The pain-catastrophizing magnification subscale was the only psychological variable to show a difference from the controls, while no significant correlations were found between any psychological measures and the clinical or psychophysic pain measures. CONCLUSIONS: There appears to be a dichotomy between somatosensory and psychological findings in the very early acute post-mTBI stage; while the first is altered and is associated with the clinical picture, the second is unchanged. In the context of the ongoing debate on the pathophysiologic nature of the post-mTBI syndrome, our findings support its "physical" basis, free of mental influence, at least in the short time window after the injury.