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Placebo-the Unknown Variable in a Controlled Trial.

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Effect of Telephone Cognitive Behavioral Therapy for Insomnia in Older Adults With Osteoarthritis Pain: A Randomized Clinical Trial.

Scalable delivery models of cognitive behavioral therapy for insomnia (CBT-I), an effective treatment, are needed for widespread implementation, particularly in rural and underserved populations lacking ready access to insomnia treatment.

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Core outcome set for pediatric chronic pain clinical trials: results from a Delphi poll and consensus meeting.

Appropriate outcome measures and high-quality intervention trials are critical to advancing care for children with chronic pain. Our aim was to update a core outcome set for pediatric chronic pain interventions. The first phase involved collecting providers', patients', and parents' perspectives about treatment of pediatric chronic pain to understand clinically meaningful outcomes to be routinely measured. The second phase was to reach consensus of mandatory and optional outcome domains following the OMERACT framework. A Modified Delphi study with two rounds was conducted including three stakeholder groups: children with chronic pain (n=93), their parents (n=90), and health care providers who treat youth with chronic pain (n=52). Quantitative and qualitative data from Round 1 of the Delphi study were summarized to identify important outcomes, which were condensed to a list of 10 outcome domains. Round 2 surveys were analyzed to determine the importance of the 10 domains and their relative ranking in each stakeholder group. A virtual consensus conference was held with the Steering committee to reach consensus on a set of recommended outcome domains for pediatric chronic pain clinical trials. It was determined, by unanimous vote, that Pain Severity, Pain Interference with Daily Living, Overall Well-being, and Adverse Events, including Death, would be considered Mandatory domains to be assessed in all trials of any type of intervention. Emotional Functioning, Physical Functioning, and Sleep were Important but optional domains. Last, the research agenda identifies several important emerging areas, including biomarkers. Future work includes selecting appropriate validated measures to assess each outcome domain.

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The Central Aspects of Pain in the Knee (CAP-Knee) questionnaire; a mixed-methods study of a self-report instrument for assessing central mechanisms in people with knee pain.

Pain is the prevailing symptom of knee osteoarthritis. Central sensitisation creates discordance between pain and joint pathology. We previously reported a central pain mechanisms trait derived from 8 discrete characteristics: neuropathic-like pain, fatigue, cognitive-impact, catastrophising, anxiety, sleep disturbance, depression, and pain distribution. We here validate and show that an 8-item questionnaire, Central Aspects of Pain in the Knee (CAP-Knee) is associated both with sensory and affective components of knee pain severity.

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Ketamine-50 years in use: from anesthesia to rapid antidepressant effects and neurobiological mechanisms.

Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More recently, ketamine has been studied and used for several new indications, ranging from chronic pain to drug addiction and post-traumatic stress disorder. The discovery of the rapid-acting antidepressant effects of ketamine has resulted in a surge of interest towards understanding the precise mechanisms driving its effects. Indeed, ketamine may have had the largest impact for advancements in the research and treatment of psychiatric disorders in the past few decades. While intense research efforts have been aimed towards uncovering the molecular targets underlying ketamine's effects in treating depression, the underlying neurobiological mechanisms remain elusive. These efforts are made more difficult by ketamine's complex dose-dependent effects on molecular mechanisms, multiple pharmacologically active metabolites, and a mechanism of action associated with the facilitation of synaptic plasticity. This review aims to provide a brief overview of the different uses of ketamine, with an emphasis on examining ketamine's rapid antidepressant effects spanning molecular, cellular, and network levels. Another focus of the review is to offer a perspective on studies related to the different doses of ketamine used in antidepressant research. Finally, the review discusses some of the latest hypotheses concerning ketamine's action.

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The relationship between sleep and opioids in chronic pain patients.

Sleep problems are common among chronic pain patients who take opioids. There are documented effects of opioids on sleep architecture; however, the long-term effects of opioids on sleep remain unknown. This study examined whether opioid-naïve participants have better sleep quality than current and previous chronic users of opioids. We also explored whether sleep differed between methadone and buprenorphine users, and whether amount of time since abstaining from opioids was associated with sleep quality.

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Mendelian randomization highlights insomnia as a risk factor for pain diagnoses.

Insomnia has been linked to acute and chronic pain conditions; however, it is unclear whether such relationships are causal. Recently, a large number of genetic variants have been discovered for both insomnia and pain through genome-wide association studies (GWAS) providing a unique opportunity to examine evidence for causal relationships through the use of the Mendelian randomization paradigm.

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Randomized clinical trial of fibromyalgia integrative training (FIT teens) for adolescents with juvenile fibromyalgia – Study design and protocol.

Juvenile-onset fibromyalgia (JFM) is a chronic debilitating pain condition that negatively impacts physical, social and academic functioning. Cognitive-behavioral therapy (CBT) is beneficial in reducing functional disability among adolescents with JFM but has only a modest impact on pain reduction and does not improve physical exercise participation. This randomized controlled trial (RCT) aims to test whether a novel intervention that combines CBT with specialized neuromuscular exercise training (the Fibromyalgia Integrative Training program for Teens "FIT Teens") is superior to CBT alone or a graded aerobic exercise (GAE) program.

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Resilience, pain, and the brain: Relationships differ by sociodemographics.

Chronic musculoskeletal (MSK) pain is disabling to individuals and burdensome to society. A relationship between telomere length and resilience was reported in individuals with consideration for chronic pain intensity. While chronic pain associates with brain changes, little is known regarding the neurobiological interface of resilience. In a group of individuals with chronic MSK pain, we examined the relationships between a previously investigated resilience index, clinical pain and functioning measures, and pain-related brain structures, with consideration for sex and ethnicity/race. A cross-sectional analysis of 166 non-Hispanic Black and non-Hispanic White adults, 45-85 years of age with pain ≥ 1 body site (s) over the past 3 months was completed. Measures of clinical pain and functioning, biobehavioral and psychosocial resilience, and structural MRI were completed. Our findings indicate higher levels of resilience associate with lower levels of clinical pain and functional limitations. Significant associations between resilience, ethnicity/race, and/or sex, and pain-related brain gray matter structure were demonstrated in the right amygdaloid complex, bilateral thalamus, and postcentral gyrus. Our findings provide compelling evidence that in order to decipher the neurobiological code of chronic pain and related protective factors, it will be important to improve how chronic pain is phenotyped; to include an equal representation of females in studies including analyses stratifying by sex, and to consider other sociodemographic factors.

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Intravenous lidocaine alleviates postherpetic neuralgia in rats via regulation of neuroinflammation of microglia and astrocytes.

This study aimed to explore the effects and possible mechanisms of intravenous lidocaine in postherpetic neuralgia (PHN) rats. Mechanical withdrawal thresholds and thermal withdrawal latencies were measured. Open field test, elevated plus maze test, and tail suspension test were used to assess anxiety- and depressive-like behaviors. Microglia and astrocytes in spinal dorsal horn (SDH), prefrontal cortex (PFC), anterior cingulate cortex (ACC), and hippocampus were analyzed. The expression of TNF-α, IL-1β, and IL-4 in SDH and serum were evaluated. Intravenous lidocaine alleviated mechanical allodynia and thermal hypoalgesia, downregulated the expression of TNF-α and IL-1β, and inhibited the activation of microglia and astrocytes in SDH. In addition, it reduced the activation of astrocyte but not microglia in PFC, ACC, and hippocampus. Intravenous lidocaine may relieve PHN by inhibiting the activation of microglia and astrocyte in SDH or by reducing the neuroinflammation and astrocyte activation in PFC, ACC, and hippocampus.

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