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: Chronic pain is a common comorbid complaint in traumatized refugees seeking treatment for posttraumatic stress disorder (PTSD) and depression. However, the effect of comorbid pain on treatment remains under investigated. : To investigate whether pre-treatment pain (severity/interference) predicts outcomes in a multimodal treatment targeting PTSD, depression, anxiety, somatic complaints, and health-related disability in refugees exposed to torture and organized violence. Additional predictors were gender, age, and number of treatment sessions. : Participants were active cases at a specialist outpatient clinic for tortured refugees (n = 276; 170 men, 106 women) who were either on a treatment waitlist (mean length = 7.4 months, SD = 4.5), in treatment (mean length = 12.2 months, SD = 6.5), or who completed treatment and had (or were waiting for) a follow-up assessment. Participants completed symptom measures at referral, pre- and post-treatment, and 9-month follow-up. Multi-level mixed modelling was used to assess whether outcomes at post-treatment and 9-months were predicted by pain, gender, age, or the number of treatment sessions. : Treatment yielded significant pre-to-post-treatment reductions in PTSD, depression, anxiety, and number of pain locations, but no reductions in pain severity/interference, or health-related disability, except for societal participation. Gains for PTSD, depression, and societal participation were maintained at the 9-month follow-up. Higher levels of pain interference (but not severity) predicted poorer outcomes (PTSD, depression, and anxiety). Age, gender and number of treatment sessions did not predict outcomes, except for a small negative effect of (older) age on PTSD. : A growing body of literature suggests that pain and PTSD symptoms interact in ways to increase the severity and impact of both disorders in refugee and non-refugee populations alike. The present study suggests interference from pain can lessen the effectiveness of standard multi-modal treatments for refugees.
Migraine is a debilitating primary headache disorder with a poorly understood aetiology. An extensive body of literature supports the theory of migraine as a systemic vascular inflammatory disorder characterised by endothelial dysfunction. It is also well-known that chronic inflammation results in an excessive burden of oxidative stress and therefore cellular dysfunction. In this study the effects of excessive oxidative stress through the phases of female migraine-with-aura (FMA) were evaluated by examining the health of the systems of haemostasis. Blood was obtained from 11 FMA patients at baseline and during the headache phase of migraine, as well as from 8 healthy age-matched female controls. Samples were analysed using thromboelastography (TEG) to evaluate viscoelastic profiles, light microscopy for erythrocyte morphology, Scanning Electron Microscopy (SEM) for erythrocyte and fibrin clot structure, confocal microscopy for β-amyloid detection in fibrin clots. Viscoelastic profiles from platelet poor plasma showed decreased clot reaction times in FMA at baseline (95% CI [5.56, 8.41]) vs. control (95% CI [7.22, 11.68]); as well as decreased time to maximum thrombus generation for the same comparison (95% CI [6.78, 10.20] vs. [8.90, 12.96]). Morphological analysis of erythrocytes indicated widespread macrocytosis, poikilocytosis and eryptosis in the migraineurs. Analysis of fibrin networks indicated that this hypercoagulability may be a result of aberrant fibrin polymerisation kinetics caused by the adoption of a β-amyloid conformation of fibrin(ogen). The results reaffirm the hypercoagulable state in migraine, and would suggest that this state is most likely a result of a systemic inflammatory state which induces oxidative damage to both erythrocytes and fibrin(ogen) in female episodic migraine-with-aura. Furthermore, if the amylodogenic changes to fibrin(ogen) were observed in a larger cohort, this would support theories of micro-embolisation in migraine-with-aura.
Many leaders in the field of chronic pain treatment consider interdisciplinary pain management programs to be the most effective treatments available for chronic pain. As programs are instituted and expanded to address demands for nonpharmacological chronic pain interventions, we need to better understand how patients experience program impacts, as well as the challenges and supports patients encounter in trying to maintain and build on intervention gains.
The brainstem plays a significant role in migraine pathogenesis, but a relationship between volume alterations of brainstem subregions and migraine aura characteristics has not been sufficiently investigated. The aim of this study is to compare the volume of the brainstem, and its subregions, between patients with a migraine with aura (MwA) and healthy controls (HC), and also to correlate characteristics of MwA and the volume of the brainstem subregions.
Generalized pain hypersensitivity is frequently observed in chronic pain conditions. Currently, identification is based on expert clinical opinion, and in very few cases combined with quantitative sensory testing. The objectives of this study were to develop and evaluate a short self-report measure of generalized pain hypersensitivity: a generalized pain questionnaire (GPQ).
The comorbidity of chronic pain and opioid addiction is a serious problem that has been growing with the practice of prescribing opioids for chronic pain. Neuroimaging research has shown that chronic pain and opioid dependence both affect brain structure and function, but this is the first study to evaluate the neurophysiological alterations in patients with comorbid chronic pain and addiction. Eighteen participants with chronic low back pain and opioid addiction were compared with eighteen age- and sex-matched healthy individuals in a pain-induction fMRI task. Unified structural equation modeling (SEM) with Lagrange multiplier (LM) testing yielded a network model of pain processing for patient and control groups based on 19 defined regions. Tests of differences between groups on specific regression parameters were determined on a path-by-path basis using -tests corrected for the number of comparisons. Patients with the chronic pain and addiction comorbidity had increased connection strengths; many of these connections were interhemispheric and spanned regions involved in sensory, affective, and cognitive processes. The affected regions included those that are commonly altered in chronic pain or addiction alone, indicating that this comorbidity manifests with neurological symptoms of both disorders. Understanding the neural mechanisms involved in the comorbidity is crucial to finding a comprehensive treatment, rather than treating the symptoms individually.
Despite the high prevalence and socioeconomic impact of chronic low back pain (cLBP), treatments for cLBP are often unsatisfactory, and effectiveness varies widely across patients. Recent neuroimaging studies have demonstrated abnormal resting-state functional connectivity (rsFC) of the default mode, salience, central executive, and sensorimotor networks in chronic pain patients, but their role as predictors of treatment responsiveness has not yet been explored. In this study, we used machine learning approaches to test if pre-treatment rsFC can predict responses to both real and sham acupuncture treatments in cLBP patients. Fifty cLBP patients participated in 4 weeks of either real (N = 24, age = 39.0 ± 12.6, 16 females) or sham acupuncture (N = 26, age = 40.0 ± 13.7, 15 females) treatment in a single-blinded trial, and a resting-state fMRI scan prior to treatment was used in data analysis. Both real and sham acupuncture can produce significant pain reduction, with those receiving real treatment experiencing greater pain relief than those receiving sham treatment. We found that pre-treatment rsFC could predict symptom changes with up to 34% and 29% variances for real and sham treatment, respectively, and the rsFC characteristics that were significantly predictive for real and sham treatment differed. These results suggest a potential way to predict treatment responses and may facilitate the development of treatment plans that optimize time, cost, and available resources.
Pain and depression have been shown to have a bidirectional interaction. Although several outcome studies have been conducted, it is still unclear if and how depression influences pain outcome. The current study aims to further clarify this relationship by comparing the predicting value of an interview- and a questionnaire-based assessment of depression.
This prospective cohort study explored whether two distinguished sensory parameters predicted acupuncture effects in chronic pain patients; namely high temporal summation of pain (TS) indicating spinal synaptic facilitation as well as a low vibration detection threshold (VDT) indicating a loss of Aβ-fiber function. Pinprick induced TS and VDT were assessed by standardized, validated methods at the most painful body site and a pain free control site in 100 chronic pain patients receiving six acupuncture sessions as part of an interdisciplinary multimodal pain treatment (IMPT). Immediate change in pain intensity after the first acupuncture session (first treatment on the first day of IMPT) was assessed by the verbal rating scale (VRS, 0-100). After 4 weeks of treatment, patients indicated in a questionnaire whether acupuncture had relieved pain immediately and whether it had contributed to overall pain reduction and well-being after IMPT. Logistic regression analysis revealed an association between high TS at the control site and a reduction in pain intensity of at least 30% (VRS) after the first acupuncture (OR [95%-CI] 4.3 [1.6-11.8]). Questionnaire ratings of immediate pain relief after acupuncture were associated with high TS at the control site (OR [95%-CI] 3.8 [1.4-10.2] any pain relief, OR [95%-CI] 5.5 [1.7-17.1] over 50% pain reduction) and at the pain site (OR [95%-CI] 3.2 [1.2-8.9] any pain relief). Appraisals of the contribution of acupuncture to overall pain reduction and well-being after IMPT were not associated with TS. The VDT was not associated with any outcome. This explorative study provides first-time evidence that high TS, especially at a pain free control site, but not VDT, might predict immediate analgesic response to acupuncture in chronic pain patients. Thus, highly centrally sensitized chronic pain patients might respond particularly well to acupuncture.
Mast cells (MCs) are present in the painful degenerate human intervertebral disc (IVD) and are associated with disease pathogenesis. MCs release granules containing enzymatic and inflammatory factors in response to stimulants or allergens. The serine protease, tryptase, is unique to MCs and its activation of the G-protein coupled receptor, Protease Activated Receptor 2 (PAR2), induces inflammation and degradation in osteoarthritic cartilage. Our previously published work has demonstrated increased levels of MC marker tryptase in IVD samples from discogenic back pain patients compared to healthy control IVD samples including expression of chemotactic agents that may facilitate MC migration into the IVD. To further elucidate MCs' role in the IVD and mechanisms underlying its effects, we investigated whether (1) human IVD cells can promote MC migration, (2) MC tryptase can mediate up-regulation of inflammatory/catabolic process in human IVD cells and tissue, and (3) the potential of PAR2 antagonist to function as a therapeutic drug in human and bovine pilot models of disease. MC migration was quantitatively assessed using conditioned media from primary human IVD cells and MC migration examined through Matrigel. Exposure to soluble IVD factors significantly enhanced MC migration, suggesting IVD cells can recruit MCs. We also demonstrated significant upregulation of MC chemokine SCF and angiogenic factor VEGFA gene expression in human IVD cells in response to recombinant human tryptase, suggesting tryptase can enhance recruitment of MCs and promotion of angiogenesis into the usually avascular IVD. Furthermore, tryptase can degrade proteoglycans in IVD tissue as demonstrated by significant increases in glycosaminoglycans released into surrounding media. This can create a catabolic microenvironment compromising structural integrity and facilitating vascular migration usually inhibited by the anti-angiogenic IVD matrix. Finally, as a "proof of concept" study, we examined the therapeutic potential of PAR2 antagonist (PAR2A) on human IVD cells and bovine organ culture IVD model. While preliminary data shows promise and points toward structural restoration of the bovine IVD including down-regulation of VEGFA, effects of PAR2 antagonist on human IVD cells differ between gender and donors suggesting that further validation is required with larger cohorts of human specimens.