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Pre-treatment pain predicts outcomes in multimodal treatment for tortured and traumatized refugees: a pilot investigation.

: 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.

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Exposure Induced Changes in Neural Circuitry for Pain-Related Fear: A Longitudinal fMRI Study in Chronic Low Back Pain.

Exposure (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.

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Sleep, Experimental Pain and Clinical Pain in Patients with Chronic Musculoskeletal Pain and Healthy Controls.

Everyday variations in night sleep in healthy pain-free subjects are at most weakly associated with pain, whereas strong alterations (eg, sleep deprivation, insomnia) lead to hyperalgesic pain changes. Since it remains unclear how substantial sleep alterations need to be in order to affect the pain system and lead to a coupling of both functions, the present study aimed at providing sufficient variance for co-variance analyses by examining a sample consisting of both healthy subjects and chronic pain patients.

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Does Sex/Gender Play a Role in Placebo and Nocebo Effects? Conflicting Evidence From Clinical Trials and Experimental Studies.

Sex has been speculated to be a predictor of the placebo and nocebo effect for many years, but whether this holds true or not has rarely been investigated. We utilized a placebo literature database on various aspects of the genuine placebo/nocebo response. In 2015, we had extracted 75 systematic reviews, meta-analyses, and meta-regressions performed in major medical areas (neurology, psychiatry, internal medicine). These meta-analyses were screened for whether sex/gender differences had been noted to contribute to the placebo/nocebo effect: in only 3 such analyses female sex was associated with a higher placebo effect, indicating poor evidence for a contribution of sex to it in RCTs. This was updated with another set of meta-analyses for the current review, but did not change the overall conclusion. The same holds true for 18 meta-analyses investigating adverse event (nocebo) reporting in RCT in the placebo arm of trials. We also screened our database for papers referring to sex/gender and the placebo effect in experimental studies, and identified 28 papers reporting 29 experiments. Their results can be summarized as follows: (a) Despite higher sensitivity of pain in females, placebo analgesia is easier to elicit in males; (b) It appears that conditioning is effective specifically eliciting nocebo effects; (c) Conditioning works specifically well to elicit placebo and nocebo effects in females and with nausea; (d) Verbal suggestions are not sufficient to induce analgesia in women, but work in men. These results will be discussed with respect to the question why nausea and pain may be prone to be responsive to sex/gender differences, while other symptoms are less. Lastly, we will discuss the apparent discrepancy between RCT with low relevance of sex, and higher relevance of sex in specific experimental settings. We argue that the placebo response is predominantly the result of a conditioning (learning) response in females, while in males it predominantly may be generated via (verbal) manipulating of expectancies. In RCT therefore, the net outcome of the intervention may be the same despite different mechanisms generating the placebo effect between the sexes, while in experimental work when both pathways are separated and explicitly explored, such differences may surface.

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Topical Review: Basic Psychological Needs in Adolescents with Chronic Pain-A Self-Determination Perspective.

This topical review outlines the resilience pathway to adaptive functioning in pediatric pain within a developmental perspective. Self-Determination Theory proposes that the satisfaction of one's basic psychological needs (for autonomy, relatedness, and competence) is crucial for understanding human flourishing and healthy development. However, the role of the basic psychological needs received little attention in a pediatric-pain population. Yet, we propose that need satisfaction may be a resilience factor and need frustration a risk factor, for living with chronic pain. In this topical review, we first discuss two major models that have been developed to understand pain-related disability: the fear-avoidance model of pain and the ecological resilience-risk model in pediatric chronic pain. Both models have been used with children and adolescents but do not include a developmental perspective. Therefore, we introduce Self-Determination Theory and highlight the potentially moderating and mediating role of the basic needs on pain-related disability in children and adolescents. Taken together, we believe that Self-Determination Theory is compatible with the fear-avoidance model of pain and the ecological resilience-risk model in pediatric chronic pain and may deepen our understanding of why some adolescents are able to live adaptively in spite of chronic pain.

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Multivariate resting-state functional connectivity predicts responses to real and sham acupuncture treatment in chronic low back pain.

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.

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Assessing Beliefs Underlying Rumination About Pain: Development and Validation of the Pain Metacognitions Questionnaire.

Metacognitions, which are beliefs about our own thinking processes, can modulate worry and rumination and thereby influence emotional distress. This study aimed to develop a self-report measure of unhelpful pain-related metacognitions which might serve as a clinical and research tool to better understand pain catastrophizing, a significant risk factor for adverse pain outcomes. Two phases of validation are presented. Phase 1 reports on how the Pain Metacognitions Questionnaire (PMQ) was empirically developed through a qualitative study of 20 people with chronic back ( = 15) or knee ( = 5) pain in secondary or tertiary care and then validated in a large internet sample of people experiencing pain ( = 864). Rasch analysis yielded a 21-item scale with two dimensions (positive and negative metacognition) assessing how useful and problematic people believe rumination about pain to be, respectively. In Phase 2, further validation using a new sample ( = 510) replicated initial findings. Both PMQ subscales have good retest reliability ( = 0.76, = 0.72) and internal consistency (0.86, 0.87). They correlate negatively with mindfulness and positively with pain intensity, disability, anxiety, depression, catastrophizing, rumination, and metacognition. The PMQ also predicts unique variance in catastrophizing when other variables are controlled and predicts 'patient' status for pain catastrophizing. Sensitivity analysis yielded preliminary suggestions for clinically meaningful cut-offs. Unhelpful pain metacognitions can be validly and reliably measured using a self-report instrument. Future studies using the PMQ might shed new light on pain-related thinking processes to develop better interventions for people prone to worry and rumination about their pain.

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Placebo and Nocebo Effects Across Symptoms: From Pain to Fatigue, Dyspnea, Nausea, and Itch.

Placebo and nocebo effects are, respectively, the helpful and harmful treatment effects that do not arise from active treatment components. These effects have thus far been researched most often in pain. It is not yet clear to what extent these findings from pain can be generalized to other somatic symptoms. This review investigates placebo and nocebo effects in four other highly prevalent symptoms: dyspnea, fatigue, nausea, and itch. The role of learning mechanisms (verbal suggestions, conditioning) in placebo and nocebo effects on various outcomes (self-reported, behavioral, and physiological) of these different somatic symptoms is explored. A search of experimental studies indicated that, as in pain, the combination of verbal suggestion and conditioning is generally more effective than suggestion alone for evoking placebo and nocebo effects. However, conditioning appears more and verbal suggestions less relevant in symptoms other than pain, with the exception of placebo effects on fatigue and nocebo effects on itch. Physiological measures, such as heart rate, lung function, or gastric activity, are rarely affected even when self-reported symptoms are. Neurobiological correlates are rarely investigated, and few commonalities appear across symptoms. Expectations generally predict placebo and nocebo effects for dyspnea and itch but seem less involved in fatigue and nausea. Individual characteristics do not consistently predict placebo or nocebo effects across symptoms or studies. In sum, many conclusions deriving from placebo and nocebo pain studies do appear to apply to other somatic symptoms, but a number of important differences exist. Understanding what type of learning mechanisms for which symptom are most likely to trigger placebo and nocebo effects is crucial for generalizing knowledge for research and therapies across symptoms and can help clinicians to optimize placebo effects in practice.

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Pain experiences and intrapersonal change among patients with chronic non-cancer pain after using a pain diary: a mixed-methods study.

Pain diaries are a valuable self-assessment tool; however, their use in chronic non-cancer pain has received limited attention. In this study, we examined the effect of pain diary use on pain intensity, interference, and intrapersonal change in patients with chronic non-cancer pain.

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Illness perception in people with primary and secondary chronic headache in the general population.

Chronic headache (headache ≥15 days/month) is a leading cause of disability. Illness perception, beliefs and cognitive models are likely central for patient understanding of their chronic pain condition and are associated with treatment outcome. However, these factors are insufficiently described in chronic headache.

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