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.

Agreement between children's, nurses' and parents' pain intensity reports is stronger before than after analgesic consumption: Results from a post-operative study.

BACKGROUND: Included in their extensive duties caring for hospitalized children, nurses are the frontline for pain assessment and treatment. Research has found that when nurses' assessments are compared with independent reports by the children or their parents, there are often differences. However, no studies have considered the contribution of analgesic medication consumption to this difference. OBJECTIVES: The aim of this study, was to assess the concordance between the pain scores recorded independently by nurses, children, and their parents both before and 1 h after analgesic consumption. DESIGN/SETTING: The trial was registered at ClinicalTrials.gov (NCT04306679) and was conducted in a post-operative inpatient facility. Following surgery, at first request of analgesic, the clinical nurses recorded the child's pain, as part of routine clinical practice. Within 10 min, the child recorded their pain level in a pain diary. At the same time, the parents separately reported their assessment of their child's pain. This process was repeated again 1 h later, when the nurses, as part of the clinical routine, recorded the children's level of post-medication pain. PARTICIPANTS: Forty-seven children ages 8-17 hospitalized for elective surgery in the General Pediatric Surgery, Orthopedics, Ear-Nose-Throat (ENT), and Oral and Maxillofacial (OM) Departments, and their parents, were included in the current report. RESULTS: The mean pain scores reported by the children were significantly higher than those reported by the nurses, both before (5.77±2.51 vs. 3.90±3.12 [mean ±SD], p <0.001) and 1 h after (3.37±2.48 vs. 0.92±2.08, p <0.001) analgesic consumption. No significant differences were found either before or after analgesic consumption in the NPS reported by the child and parent. Agreement between the NPS scores reported by the child and nurses was good before (ICC = 0.754, p <0.001) and only moderate 1 h after (ICC = 0.504, p = 0.017) analgesic consumption. Similarly, agreement between the NPS scores reported by the child and parents was good before (ICC = 0.855, p <0.001) and only moderate 1 h after (ICC = 0.722, p <0.001) analgesic consumption. CONCLUSIONS: While self-report measures remain the gold standard for pediatric pain care, the results of this study suggest that after analgesic administration, agreement between children's and nurses' assessments, and between children's and parents' assessments of pain deteriorated. Our results further confirm that proxy assessments recorded by parents are closer to their children's assessments than are those of nurses and should consequently be preferred especially after analgesic consumption.

Temporal Summation Predicts De Novo Contralateral Pain After Cordotomy in Patients With Refractory Cancer Pain.

BACKGROUND: Percutaneous cervical cordotomy (PCC), which selectively interrupts ascending nociceptive pathways in the spinal cord, can mitigate severe refractory cancer pain. It has an impressive success rate, with most patients emerging pain-free. Aside from the usual complications of neurosurgical procedures, the risks of PCC include development of contralateral pain, which is less understood. OBJECTIVE: To evaluate whether sensory and pain sensitivity, as measured by quantitative sensory testing (QST), are associated with PCC clinical outcomes. METHODS: Fourteen palliative care cancer patients with severe chronic refractory pain limited mainly to one side of the body underwent comprehensive quantitative sensory testing assessment pre-PPC and post-PCC. They were also queried about maximal pain during the 24 h precordotomy (0-10 numerical pain scale). RESULTS: All 14 patients reported reduced pain postcordotomy, with 7 reporting complete resolution. Four patients reported de novo contralateral pain. Reduced sensitivity in sensory and pain thresholds to heat and mechanical stimuli was recorded on the operated side (P = .028). Sensitivity to mechanical pressure increased on the unaffected side (P = .023), whereas other sensory thresholds were unchanged. The presurgical temporal summation values predicted postoperative contralateral pain (r = 0.582, P = .037). CONCLUSION: The development of contralateral pain in patients postcordotomy for cancer pain might be due to central sensitization. Temporal summation could serve as a potential screening tool to identify those who are most likely at risk to develop contralateral pain. Analysis of PCC affords a unique opportunity to investigate how a specific lesion to the nociceptive system affects pain processes.

Dispositional and situational personal features and acute post-collision head and neck pain: Double mediation of pain catastrophizing and pain sensitivity.

Pain variability can be partially attributed to psycho-cognitive features involved in its processing. However, accumulating research suggests that simple linear correlation between situational and dispositional factors may not be sufficiently explanatory, with some positing a role for mediating influences. In addition, acute pain processing studies generally focus on a post-operative model with less attention provided to post-traumatic injury. As such, this study aimed to investigate a more comprehensive pain processing model that included direct and indirect associations between acute pain intensity in the head and neck, pain catastrophizing (using pain catastrophizing scale (PCS)), and pain sensitivity (using the pain sensitivity questionnaire (PSQ)), among 239 patients with post-motor vehicle collision pain. The effect of personality traits (using Ten Items Personality Inventory (TIPI)) and emotional status (using Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS)) on that model was examined as well. To this end, three Structural Equation Modeling (SEM) analyses were conducted. Overall, the data had good fit to all the models, with only PSQ found to have a direct correlation with acute pain intensity. The SEM analyses conversely revealed several mediations. Specifically, that: first, PSQ fully mediated the relationship between PCS and pain intensity; second, PCS and PSQ together fully mediated the relationship between conscientiousness (personality trait) and pain intensity; and finally, emotional status had direct and indirect links with PSQ and pain intensity. In conclusion, these models suggest that during the acute post-collision phase, pain sensitivity intermediates between emotional states and personality traits, partially via elevated pain catastrophizing thoughts.

The role of itch and pain modulation in the prediction of phototherapy outcomes: a prospective cohort study.

OBJECTIVES: Ability to predict which chronic itch patients will benefit from particular treatments is a challenge. Common features in itch and pain in respect to sensory elicitation, and mechanisms of processing including sensitization and inhibition at the peripheral and central levels, may serve to understand variability in treatment outcomes. As such this study aimed to explore whether phototherapy outcomes can be predicted by psychophysical parameters of pain and itch modulatory processing. METHODS: Prospective cohort study on chronic-itch patients (n = 44) assessed before 20 treatments of NB UVB. Level of itch and pain reduction following painful stimulation (reflecting the 'pain inhibits pain' phenomenon) used to assess the top-down modulation response efficacy. Magnitude of Conditioned Pain Modulation (CPM) for itch (CPM-itch) and for pain (CPM-pain) (reflecting inhibition) and magnitude of temporal summation (TS) of pain (reflecting ascending facilitation pathways) assessed to predict treatment effect. RESULTS: Higher improvement of itch symptoms following phototherapy was correlated with more efficient CPM-itch (r = 0.62, p < .001), but not magnitude of CPM-pain or level of temporal summation. DISCUSSION: Findings emphasize the role of descending inhibition pathways in determining phototherapy efficacy in chronic itch patients. Such an evaluation-based approach may contribute to better patient selection for phototherapy improving patients' disease outcomes.

Effects of Pain-Reporting Education Program on Children's Pain Reports-Results From a Randomized Controlled Post-operative Pediatric Pain Trial.

Objective: Accurate assessment of patients' pain is an essential part of adequate analgesic treatment. Although reporting pain is a complex task, limited-to-no instructions are provided to pediatric patients regarding this process. Our goal in this randomized parallel-group clinical trial (Clinicaltrial.gov study protocol number NCT04306679) was to evaluate if a training program designed to improve children's ability to understand and use pain scales in a post-surgical setting would affect their pain scores. Methods: Eligible children (aged 8-17), hospitalized for elective surgery and their parents were randomized into two groups. Pre-surgery the intervention group underwent a multi-media program aimed to teach and train how to report pain. The control group received standard pre-surgical instructions. Post-surgery, the children reported their pain on 4 pain scales. The primary outcome was the concordance between children's pain intensity scores reported on four pain scales, both in terms of within-child standard deviation and absolute difference. Results: Ninety-six children met inclusion criteria and completed the study. The trained subjects' pain reports had significantly (p = 0.002) lower within-subject standard deviation (0.41 ± 0.31) than the control group (0.67 ± 0.46). In line, regarding absolute difference, the concordance of children's pain reports was twice better in the trained group (mean difference of 0.43 ± 0.40) than in the control group (0.88 ± 0.70) (p < 0.001). Discussion: Our results suggests that children's ability to report pain is a skill that can be improved. Future studies should test the potential clinical impacts of educational interventions aimed to improve pain assessment in children and adults.

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.

Additive Analgesic Effect of Transcranial Direct Current Stimulation Together with Mirror Therapy for the Treatment of Phantom Pain.

OBJECTIVE: Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation. DESIGN: Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2 weeks (once daily): 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1 week, 1 month, and 3 months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory. RESULTS: Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P<0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings. CONCLUSIONS: Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.

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.

Monitoring Migraine Cycle Dynamics with an Easy-to-Use Electrophysiological Marker-A Pilot Study.

Migraine attacks can cause significant discomfort and reduced functioning for days at a time, including the pre-ictal and post-ictal periods. During the inter-ictsal period, however, migraineurs seem to function normally. It is puzzling, therefore, that event-related potentials of migraine patients often differ in the asymptomatic and inter-ictal period. Part of the electrophysiological dynamics demonstrated in the migraine cycle are attention related. In this pilot study we evaluated an easy-to-use new marker, the Brain Engagement Index (BEI), for attention monitoring during the migraine cycle. We sampled 12 migraine patients for 20 days within one calendar month. Each session consisted of subjects' reports of stress level and migraine-related symptoms, and a 5 min EEG recording, with a 2-electrode EEG device, during an auditory oddball task. The first minute of the EEG sample was analyzed. Repetitive samples were also obtained from 10 healthy controls. The brain engagement index increased significantly during the pre-ictal (p ≈ 0.001) and the ictal (p ≈ 0.020) periods compared with the inter-ictal period. No difference was observed between the pre-ictal and ictal periods. Control subjects demonstrated intermediate Brain Engagement Index values, that is, higher than inter-ictal, yet lower than pre-ictal. Our preliminary results demonstrate the potential advantage of the use of a simple EEG system for improved prediction of migraine attacks. Further study is required to evaluate the efficacy of the Brain Engagement Index in monitoring the migraine cycle and the possible effects of interventions.

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.