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Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or prior experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo response in chronic low back pain using over 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not treated). Utilizing a nested leave-one-out cross-validated approach, we distinguished placebo responders from non-responders with 79% accuracy using language features alone; a subset of these features – semantic distances to identity and stigma and the number of achievement-related words – also explained 46% of the variance in placebo analgesia. Importantly, these language features were not due to generic treatment effects and were associated with patients' specific baseline psychological traits previously shown to be predictive of placebo including awareness and personality characteristics, explaining an additional 31% of the variance in placebo analgesia beyond that of personality. Initial interpretation of the features suggests that placebo responders differed in how they talked about negative emotions and the extent that they expressed awareness to various aspects of their experiences; differences were also seen in time spent talking about leisure activities. These results indicate that patients' language is sufficient to identify placebo response and implies that specific speech features may be predictive of responders prior to treatment.
Learn More >Chronic pain is theoretically conceptualized from a biopsychosocial perspective. However, research into chronic pain still tends to focus on isolated, biological, psychological, or social variables. Simultaneous examination of these variables in the prediction of outcomes is important because communalities between predictors exist. Examination of unique contributions might help guide research and interventions in a more effective way.
Learn More >The Avoidance-Endurance Fast-Screen (AEFS) is a 9-item self-report questionnaire that classifies patients with back pain into four activity-related subgroups, based on the avoidance-endurance model (AEM) of pain. The objective of this study was to translate the AEFS into Danish and investigate its discriminative abilities in a large, diverse patient sample.
Learn More >Youth with chronic pain and youth who have experienced stressors are at risk for poor outcomes; however, little is known about the intersection of pain and stressors. This study aims to understand the prevalence of stressors among youth with chronic pain and the relationship between stressors and pain-related outcomes. Seven hundred and seventy youth with chronic pain aged 8-18 (M = 14.15 years, 70% female) reported pain characteristics, stressors, anxiety, disability, and quality of life. Most participants (82%) endorsed at least one stressor. A greater number of stressors was significantly related to greater anxiety and disability, and lower levels of quality of life. School stressors were significantly associated with functional disability; family, school, and peer stressors were significantly associated with anxiety and quality of life. Stressors are common in youth with chronic pain, and the presence of stressors is related to greater functional impairment. The results of this preliminary study using semi-structured clinical interviews suggest the importance of developing a validated measure that encompasses a wide variety of stressors for youth with pain. Future research on patient-reported stressors, relative intensity, and impact are needed.
Learn More >Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache and various neurological symptoms. Migraine is typically treated by pharmacological or non-pharmacological therapies to relieve pain or prevent migraine attacks. Pharmacological therapies show limited efficacy in relieving headache and are often accompanied by adverse effects, while the benefits of acupuncture, a non-pharmacological therapy, have been well-documented in both the treatment and prevention of acute migraine attacks. However, the underlying mechanism of the effect of acupuncture on relieving migraine remains unclear. Recent advances in neuroimaging technology have offered new opportunities to explore the underlying neural mechanism of acupuncture in treating migraine. To pave the way for future research, this review provides an overview neuroimaging studies on the use of acupuncture for migraine in the last 10 years. Using search terms about acupuncture, neuroimaging and migraine, we searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure from January 2009 to June 2020 for neuroimaging studies that examined the effect of acupuncture in migraine. All published randomized and non-randomized controlled neuroimaging studies were included. We summarized the proposed neural mechanism underlying acupuncture analgesia in acute migraine, and the proposed neural mechanism underlying the sustained effect of acupuncture in migraine prophylaxis. A total of 619 articles were retrieved. After removing reviews, meta-analyses, animal studies and etc., 15 articles were eligible and included in this review. The methods used were positron emission computed tomography (PET-CT; = 2 studies), magnetic resonance spectroscopy ( = 1), and functional magnetic resonance imaging (fMRI; = 12). The analyses used included the regional homogeneity (ReHo) method (n = 3), amplitude of low frequency (ALFF) method ( = 2), independent component analysis (ICA; = 3), seed-based analysis (SBA; = 1), both ICA and SBA ( = 1), Pearson's correlation to calculate functional connectivity (FC) between brain regions ( = 1), and a machine learning method ( = 1). Five studies focused on the instant effect of acupuncture, and the research objects were those with acute migraine ( = 2) and migraine in the interictal phase ( = 3). Ten studies focused on the lasting effect of acupuncture, and all the studies selected migraine patients in the interictal phase. This review included five task-based studies and 10 resting-state studies. None of the studies conducted a correlation analysis between functional brain changes and instant clinical efficacy. For studies that performed a correlation analysis between functional brain changes and sustained clinical efficacy, the prophylactic effect of acupuncture on migraine might be through regulation of the visual network, default mode network (DMN), sensory motor network, frontoparietal network (FPN), limbic system, and/or descending pain modulatory system (DPMS). The neural mechanism underlying the immediate effect of acupuncture analgesia remains unclear, and the neural mechanism of sustained acupuncture treatment for migraine might be related to the regulation of pain-related brain networks. The experimental design of neuroimaging studies that examined the effect of acupuncture in migraine also have some shortcomings, and it is necessary to standardize and optimize the experimental design. Multi-center neuroimaging studies are needed to provide a better insight into the neural mechanism underlying the effect of acupuncture on migraine. Multi-modality neuroimaging studies that integrate multiple data analysis methods are required for cross-validation of the neuroimaging results. In addition, applying machine learning methods in neuroimaging studies can help to predict acupuncture efficacy and screen for migraineurs for whom acupuncture treatment would be suitable.
Learn More >Placebo and nocebo effects in pain are well documented. One leading explanation is that instructions indicating that pain will either increase or decrease after receipt of a treatment give rise to expectations for increased or decreased pain. However, the psychological mechanisms through which expectations affect pain perception are not well understood. One possibility is that the expectation of increased pain leads to anticipatory anxiety, which in turn increases attention towards painful sensations.
Learn More >Fibromyalgia is a chronic condition characterised by widespread musculoskeletal pain. Although accumulating evidence suggests that exposure to stressful events increases the risk for this complex disorder, this is the first meta-analysis to compare the impact of a full range of lifetime stressors (e.g. physical trauma through to emotional neglect) on adult fibromyalgia.
Learn More >Epidural injections have been extensively used since their description in 1901, and steroids since their first utilization in 1952. Multiple randomized controlled trials and systematic reviews have reached discordant conclusions regarding the effectiveness of sodium chloride solution and steroids in managing spinal pain. True placebo-controlled trials with the injection of an inactive substance to unrelated structures have been nonexistent. Consequently, the discussions continue to escalate, seemingly without proper discourse. In this review, we sought to assess the true placebo nature of saline and the effectiveness of steroids.
Learn More >Chronic widespread pain (CWP) including fibromyalgia has a prevalence of up to 15% and is associated with substantial morbidity. Supporting psychosocial and behavioural self-management is increasingly important for CWP, as pharmacological interventions show limited benefit. We systematically reviewed the effectiveness of interventions applying self-management principles for CWP including fibromyalgia.
Learn More >Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC arrays and analyzed. Multiple testing correction was performed using the Bonferroni method and 10% false discovery rate (FDR). We validated 11 candidate genes previously associated with PTSD including , , and 1. In the epigenome-wide scan, seven novel CpGs were significantly associated with PTSD within/near , , , , , and , with all CpGs except the CpG hypermethylated in PTSD. These results were significantly enriched for genes whose DNA methylation was previously associated with migraine (-value = 0.036). At 10% FDR, 132 CpGs in 99 genes associated with PTSD were also associated with migraine in the migraine twin samples. Genes associated with PTSD were overrepresented in vascular smooth muscle, axon guidance and oxytocin signaling pathways, while genes associated with both PTSD and migraine were enriched for AMPK signaling and longevity regulating pathways. In conclusion, these results suggest that common genes and pathways are likely involved in PTSD and migraine, explaining at least in part the co-morbidity between the two disorders.
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