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The neural processes of acquiring placebo effects through observation.

Learning through social observation is critical for humans. The present study investigates the neural processes underlying the acquisition of placebo effects through observational learning. We created a new functional magnetic resonance imaging (fMRI) paradigm where participants (n = 38, healthy, both sexes) observed a demonstrator experiencing pain relief by a placebo treatment cream and experiencing pain without a treatment (control cream), and subsequently performed the same procedure themselves. Participants demonstrated placebo hypoalgesia while they performed the procedure themselves, confirming that observational learning can lead to placebo effects. During the observational learning phase, fMRI analysis showed a modulation of the amygdalae, periaqueductal grey, temporoparietal junctions (TPJ), and dorsolateral prefrontal cortex (DLPFC). Connectivity between the DLPFC and TPJ during the observational learning task was modulated by the placebo treatment and predicted subsequent placebo effects. Mediation analysis further confirmed that the DLPFC-TPJ connectivity formally mediated the effect of the observed treatment condition on subsequent placebo effects. Additionally, pre-recorded resting state connectivity between the DLPFC and TPJ also predicted observationally-learned placebo effects. Our findings provide an understanding of the neural processes during the acquisition of placebo effects through observation and indicate a critical role for DLPFC-TPJ integration processes during observational learning of therapeutic outcomes.

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Efficacy and Safety of Multiple Dupilumab Dose Regimens After Initial Successful Treatment in Patients With Atopic Dermatitis: A Randomized Clinical Trial.

The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD).

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Pain stickiness in pediatric complex regional pain syndrome: A role for the nucleus accumbens.

Some individuals with chronic pain experience improvement in their pain with treatment, whereas others do not. The neurobiological reason is unclear, but an understanding of brain structure and functional patterns may provide insights into pain's responsivity to treatment. In this investigation, we used magnetic resonance imaging (MRI) techniques to determine grey matter density alterations on resting functional connectivity (RFC) strengths between pain responders and nonresponders in patients with complex regional pain syndrome. Brain metrics of pediatric patients at admission to an intensive pain rehabilitative treatment program were evaluated. Pain responders reported significant pain improvement at discharge and/or follow-up whereas nonresponders reported no improvements in pain, increases in pain, or emergence of new pain symptoms. The pain (responder/nonresponder) groups were compared with pain-free healthy controls to examine predictors of pain responder status via brain metrics. Our results show: (1) on admission, pain nonresponders had decreased grey matter density (GMD) within the nucleus accumbens (NAc) and reduced RFC strength between the NAc and the dorsolateral prefrontal cortex vs. responders; (2) Connectivity strength was positively correlated with change in pain intensity from admission to discharge; (3) Compared with pain-free controls, grey matter and RFC differences emerged only among pain nonresponders; and (4) Using a discriminative model, combining GMD and RFC strengths assessed at admission showed the highest prediction estimate (87%) on potential for pain improvement, warranting testing in a de novo sample. Taken together, these results support the idea that treatment responsiveness on pain is underpinned by concurrent brain structure and resting brain activity.

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Confirmatory factor analysis of the International Pain Outcome questionnaire in surgery.

Choosing perioperative suitable treatments requires reliable and valid outcome measurements. The International Pain Outcome (IPO) questionnaire has been widely used for quality improvement and research purposes within the PAIN-OUT network that has collected more than 550,000 data sets of postoperative patients in 200 hospitals worldwide. Our aim is to confirm psychometric properties of the Spanish version of the IPO questionnaire and its invariance by pain predictors.

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Preliminary evidence for conserved transcriptional response to adversity in adults with temporomandibular disorder.

Temporomandibular disorder (TMD) is one of the most common orofacial pain conditions. Alteration in immune functioning is one promising biological mechanism underlying pain in TMD. However, there is a gap in the understanding of molecular bases contributing to altered immune functioning in these patients.

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Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial.

To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions.

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Identification of DNA methylation associated enrichment pathways in adults with non-specific chronic low back pain.

Chronic low back pain (cLBP) that cannot be attributable to a specific pathoanatomical change is associated with high personal and societal costs. Still, the underlying mechanism that causes and sustains such a phenotype is largely unknown. Emerging evidence suggests that epigenetic changes play a role in chronic pain conditions. Using reduced representation bisulfite sequencing (RRBS), we evaluated DNA methylation profiles of adults with non-specific cLBP (n = 50) and pain-free controls (n = 48). We identified 28,325 hypermethylated and 36,936 hypomethylated CpG sites (p < 0.05). After correcting for multiple testing, we identified 159 DMRs (q < 0.01and methylation difference > 10%), the majority of which were located in CpG island (50%) and promoter regions (48%) on the associated genes. The genes associated with the differentially methylated regions were highly enriched in biological processes that have previously been implicated in immune signaling, endochondral ossification, and G-protein coupled transmissions. Our findings support inflammatory alterations and the role of bone maturation in cLBP. This study suggests that epigenetic regulation has an important role in the pathophysiology of non-specific cLBP and a basis for future studies in biomarker development and targeted interventions.

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Long-term opioid therapy for chronic noncancer pain: second update of the German guidelines.

The opioid epidemic in North America challenges national guidelines worldwide to define the importance of opioids for the management of chronic noncancer pain (CNCP).

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A Phenomenological Exploration of the Personal Implications of Female Adolescents Living With Chronic Pain.

Chronic pain (CP) negatively impacts everyday previously taken-for-granted activities resulting in considerable psychosocial stress for the individual. Qualitative research in pediatric CP is limited despite the considerable influence CP has on the process of establishing one's personal identity during these formative years and invites the opportunity to understand how CP affects these young individuals from their perspective. The objective of the study was to inquire into the experiences of female adolescents living with CP in order to enhance our understanding of how CP affects their personal lives.

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Transcranial direct current stimulation in inflammatory bowel disease patients modifies resting-state functional connectivity: A RCT.

Chronic pain is known to be associated with functional and structural changes in the brain. Inflammatory bowel disease (IBD) presents with chronic abdominal pain in almost 35% of all patients. This study investigates structural and functional changes in magnetic resonance imaging (MRI) after transcranial direct current stimulation (tDCS) applied to ameliorate pain in IBD.

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