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The associations between loneliness, social exclusion and pain in the general population: A N=502,528 cross-sectional UK Biobank study.

Chronic pain presents a huge burden for individuals and society and evidence suggests intrinsic links with loneliness, social exclusion and sleep. Research examining how these factors interact is warranted. We aimed to explore the relationships between social exclusion, loneliness, acute and chronic pain, and the influence of poor sleep, in the general UK population. A cross-sectional analysis of UKBiobank participants with baseline data for acute and chronic pain, loneliness and sleep. Principal components analysis (PCA) used data relating to social isolation and deprivation to establish a composite measure of social exclusion. Binary logistic regression analyses were performed. 502,528 UKBiobank participants (mean age = 56.6years, 54.4%female, 94.6%white) were included in the analysis. PCA suggested three social exclusion factors "social participation", "individual deprivation" and "area deprivation". Loneliness significantly predicted acute (OR:1.887; 95%CI1.857-1.917) and chronic pain (OR:1.843; 95%CI1.816-1.870). Each social exclusion factor alone and in combination significantly predicted pain with largest effects for individuals scoring high on all social exclusion factors, for acute (OR:2.087; 95%CI2.026-2.150) and chronic (OR:2.314; 95%CI2.249-2.380) pain. Coefficients remained statistically significant when models were adjusted for demographics and sleep. Social exclusion (as a multifaceted construct) and loneliness are associated with an increased prevalence of acute and chronic pain. Poor sleep has a potential mediating effect on these associations. Exploration of the incidence of pain in loneliness and social exclusion in the general population is warranted. From a public health perspective these findings could be used to design social interventions to prevent or manage pain and mitigate social exclusion.

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Placebo hypoalgesia: racial differences.

No large-cohort studies that examine potential racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic pain participants self-identified as either African American/black (AA/black) or white. We enrolled 372 study participants, 186 with a diagnosis of temporomandibular disorder (TMD) and 186 race-, sex-, and age-matched healthy participants to participate in a placebo experiment. Using a well-established paradigm of classical conditioning with verbal suggestions, each individual pain sensitivity was measured to calibrate the temperatures for high- and low-pain stimuli in the conditioning protocol. These 2 temperatures were then paired with a red and green screen, respectively, and participants were told that the analgesic intervention would activate during the green screens to reduce pain. Participants then rated the painfulness of each stimulus on a visual analog scale ranging from 0 to 100. Racial influences were tested on conditioning strength, reinforced expectations, and placebo hypoalgesia. We found that white participants reported greater conditioning effects, reinforced relief expectations, and placebo effects when compared with their AA/black counterparts. Racial effects on placebo were observed in TMD, although negligible, short-lasting, and mediated by conditioning strength. Secondary analyses on the effect of experimenter-participant race and sex concordance indicated that same experimenter-participant race induced greater placebo hypoalgesia in TMDs while different sex induced greater placebo hypoalgesia in healthy participants. This is the first and largest study to analyze racial effects on placebo hypoalgesia and has implications for both clinical research and treatment outcomes.

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Sex differences in the development of anxiodepressive-like behavior of mice subjected to sciatic nerve cuffing.

We investigated the contribution of nucleus locus ceruleus (LC) to the development of pain-associated affective behavior. Mice of both sexes were subjected to sciatic nerve cuffing, a model of peripheral nerve injury, and monitored for 45 days. Although the thermal and mechanical thresholds were equally decreased in both males and females, only the male mice developed anxiodepressive-like behavior, which was complemented by suppressed hippocampal neurogenesis. Furthermore, the LC activity was lower in males when compared with females subjected to sciatic cuffing. Next, we used a chemogenetic approach to modulate the activity of LC projections to the dentate gyrus of the hippocampus in females without cuffs and in males with sciatic cuffs. Sustained inhibition of the LC projections to the dentate gyrus for 15 days induced anxiodepressive-like behavior and reduced the hippocampal neurogenesis in females. Activation of the LC projections to the dentate gyrus for 15 days prevented the development of anxiodepressive-like behavior and increased the hippocampal neurogenesis in males with cuffs. In sum, we demonstrated that the LC projections to the hippocampus link the sensory to the affective component of neuropathic injury and that the female mice are able to dissociate the nociception from affect by maintaining robust LC activity. The work provides evidence that sex differences in LC response to pain determine the sex differences in the development of pain phenotype.

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Extended overview of the longitudinal pain-depression association: A comparison of six cohorts treated for specific chronic pain conditions.

The aim was to quantify and to compare the associations between longitudinal changes in pain and depression in different chronic pain conditions.

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Enhanced mindfulness-based stress reduction in episodic migraine: a randomized clinical trial with magnetic resonance imaging outcomes.

We aimed to evaluate the efficacy of an enhanced mindfulness-based stress reduction (MBSR+) vs stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n = 50) with SMH (n = 48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then biweekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. Magnetic resonance imaging (MRI) outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula to DLPFC and cognitive task network, and gray matter volume of DLPFC, dorsal anterior insula, and anterior midcingulate. Secondary outcomes were headache-related disability, pain severity, response to treatment, migraine days, and MRI whole-brain analyses. Reduction in headache days from baseline to 20 weeks was greater for MBSR+ (7.8 [95% CI, 6.9-8.8] to 4.6 [95% CI, 3.7-5.6]) than for SMH (7.7 [95% CI 6.7-8.7] to 6.0 [95% CI, 4.9-7.0]) (P = 0.04). Fifty-two percent of the MBSR+ group showed a response to treatment (50% reduction in headache days) compared with 23% in the SMH group (P = 0.004). Reduction in headache-related disability was greater for MBSR+ (59.6 [95% CI, 57.9-61.3] to 54.6 [95% CI, 52.9-56.4]) than SMH (59.6 [95% CI, 57.7-61.5] to 57.5 [95% CI, 55.5-59.4]) (P = 0.02). There were no differences in clinical outcomes at 52 weeks or MRI outcomes at 20 weeks, although changes related to cognitive networks with MBSR+ were observed. Enhanced mindfulness-based stress reduction is an effective treatment option for episodic migraine.

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Patients’ experience with and perspectives on neuromodulation for pain: a systematic review of the qualitative research literature.

Chronic pain has far-reaching impacts on a person's life and on society more broadly. After failure or intolerance of conservative treatments, neuromodulation may be an option for a subgroup of patients. However, little is known about the patient experience of neuromodulation. We conducted a systematic review of published qualitative research on patient experience with neuromodulation for chronic pain. Four databases were searched: MEDLINE, EMBASE, Psych INFO, and all EMB reviews, from inception to December 4, 2019. We used narrative synthesis to identify key findings from the included studies. The data were qualitatively analyzed using a modified constant comparative analysis to identify key themes across the studies. Seven thousand five hundred forty-two unique citations were retrieved. Sixty-four abstracts were selected by the reviewers and continued to full-text review. After full-text review, 57 studies were excluded with 7 studies included in this systematic review. The included studies were of high quality. Four broad themes emerged: (1) living with chronic pain, (2) expectations, (3) managing challenges, and (4) regaining normalcy. Neuromodulation should be part of an overall pain management plan that may include the need for ongoing emotional and psychosocial support. A deeper knowledge of the patient experience with neuromodulation will assist care teams in providing meaningful support to patients. The results of this study suggest that further research is needed to support neuromodulation as an option for patients living with chronic pain.

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Comparative Effectiveness of Cognitive Behavioral Therapy for Chronic Pain and Chronic Pain Self-Management within the Context of Voluntary Patient-Centered Prescription Opioid Tapering: The EMPOWER Study Protocol.

Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology.

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The mindful migraine: does mindfulness-based stress reduction relieve episodic migraine?

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Opioid Exposure Negatively Affects Antidepressant Response to Venlafaxine in Older Adults with Chronic Low Back Pain and Depression.

Serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly co-prescribed with opioids for chronic pain. The purpose of this study was to describe pain and mood response to venlafaxine among older adults with chronic low back pain (CLBP) and depression relative to opioid exposure.

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Interrelations between pain, stress and executive functioning.

The purpose of this narrative review is to discuss the interrelations between pain, stress and executive functions.

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