Bumblebee nest departures under low light conditions at sunrise and sunset.

Only a few diurnal animals, such as bumblebees, extend their activity into the time around sunrise and sunset when illumination levels are low. Low light impairs viewing conditions and increases sensory costs, but whether diurnal insects use low light as a cue to make behavioural decisions is uncertain. To investigate how they decide to initiate foraging at these times of day, we observed bumblebee nest-departure behaviours inside a flight net, under naturally changing light conditions. In brighter light bees did not attempt to return to the nest and departed with minimal delay, as expected. In low light the probability of non-departures increased, as a small number of bees attempted to return after spending time on the departure platform. Additionally, in lower illumination bees spent more time on the platform before flying away, up to 68 s. Our results suggest that bees may assess light conditions once outside the colony to inform the decision to depart. These findings give novel insights into how behavioural decisions are made at the start and the end of a foraging day in diurnal animals when the limits of their vision impose additional costs on foraging efficiency.

Elevated pain sensitivity is associated with reduced REM sleep in females with comorbid temporomandibular disorder and insomnia.

OBJECTIVE: Patients with chronic pain disorders, including Temporomandibular Disorders (TMDs) endorse high levels of sleep disturbances, frequently reporting reduced sleep quality. Despite this, little is known about the effect that daytime pain has on the microstructure and macro-architecture of sleep. Therefore, we aimed to examine the extent to which daytime pain sensitivity, measured using quantitative sensory testing (QST), is associated with objective sleep parameters the following night, including sleep architecture and power spectral density, in women with TMD. METHODS: : 144 females with myalgia and arthralgia by examination using the Diagnostic criteria for TMD completed a comprehensive QST battery consisting of General Pain Sensitivity, Central Sensitization Index, and Masseter Pressure Pain Threshold assessments. Polysomnography (PSG) was collected the same night to measure sleep architecture and calculate relative power in delta, theta, alpha, sigma, and beta power bands. RESULTS: Central Sensitization (B= -3.069, P = 0.009), General Pain Sensitivity Indices (B= -3.069, P = 0.007), and Masseter Pain Pressure Threshold (B = 0.030, P = 0.008) were significantly associated with lower REM% both before and after controlling for covariates. Pain sensitivity measures were not significantly associated with relative power in any of the spectral bands, nor with any other sleep architectural stages. CONCLUSIONS: Our findings demonstrate that higher generalized pain sensitivity, masseter pain pressure threshold, as well as central sensitization were associated with a lower percentage of REM in participants with myofascial pain and arthralgia of the masticatory system. These findings provide an important step toward understanding the mechanistic underpinnings of how chronic pain interacts with sleep physiology.

Suvorexant alters dynamics of the sleep-electroencephalography-power spectrum and depressive-symptom trajectories during inpatient opioid withdrawal.

STUDY OBJECTIVES: Opioid withdrawal is an aversive experience that often exacerbates depressive symptoms and poor sleep. The aims of the present study were to examine the effects of suvorexant on oscillatory sleep-electroencephalography (EEG) band power during medically managed opioid withdrawal, and to examine their association with withdrawal severity and depressive symptoms. METHODS: Participants with opioid use disorder (N = 38: age-range:21-63, 87% male, 45% white) underwent an 11-day buprenorphine taper, in which they were randomly assigned to suvorexant (20 mg [n = 14] or 40 mg [n = 12]), or placebo [n = 12], while ambulatory sleep-EEG data was collected. Linear mixed-effect models were used to explore: (1) main and interactive effects of drug group, and time on sleep-EEG band power, and (2) associations between sleep-EEG band power change, depressive symptoms, and withdrawal severity. RESULTS: Oscillatory spectral power tended to be greater in the suvorexant groups. Over the course of the study, decreases in delta power were observed in all study groups (ß = -189.082, d = -0.522, p = <0.005), increases in beta power (20 mg: ß = 2.579, d = 0.413, p = 0.009 | 40 mg ß = 5.265, d = 0.847, p < 0.001) alpha power (20 mg: ß = 158.304, d = 0.397, p = 0.009 | 40 mg: ß = 250.212, d = 0.601, p = 0.001) and sigma power (20 mg: ß = 48.97, d = 0.410, p < 0.001 | 40 mg: ß = 71.54, d = 0.568, p < 0.001) were observed in the two suvorexant groups. During the four-night taper, decreases in delta power were associated with decreases in depressive symptoms (20 mg: ß = 190.90, d = 0.308, p = 0.99 | 40 mg: ß = 433.33, d = 0.889 p = <0.001), and withdrawal severity (20 mg: ß = 215.55, d = 0.034, p = 0.006 | 40 mg: ß = 192.64, d = -0.854, p = <0.001), in both suvorexant groups and increases in sigma power were associated with decreases in withdrawal severity (20 mg: ß = -357.84, d = -0.659, p = 0.004 | 40 mg: ß = -906.35, d = -1.053, p = <0.001). Post-taper decreases in delta (20 mg: ß = 740.58, d = 0.964 p = <0.001 | 40 mg: ß = 662.23, d = 0.882, p = <0.001) and sigma power (20 mg only: ß = 335.54, d = 0.560, p = 0.023) were associated with reduced depressive symptoms in the placebo group. CONCLUSIONS: Results highlight a complex and nuanced relationship between sleep-EEG power and symptoms of depression and withdrawal. Changes in delta power may represent a mechanism influencing depressive symptoms and withdrawal.

A Preliminary Examination of the Effects and Mechanisms of Cognitive Behavioral Therapy for Insomnia on Systemic Inflammation Among Patients with Knee Osteoarthritis.

BACKGROUND: Systemic inflammation, particularly the elevation of interleukin-6 (IL-6), plays an important role in the maintenance and progression of knee osteoarthritis. Insomnia, being highly prevalent in knee osteoarthritis, is understood to be a risk factor for systemic inflammation. The present study examined if cognitive behavioral therapy for insomnia (CBT-I) would reduce circulating IL-6 levels to a larger extent than the active control condition via greater improvement in sleep maintenance disturbance at mid-treatment, among individuals with knee osteoarthritis and insomnia disorder. METHODS: This is an ancillary study (N = 64) from a larger double-blind, randomized, active controlled clinical trial. Serum IL-6 was measured at baseline, post-treatment, and 3- and 6-month follow-ups. Sleep was measured by daily sleep diaries. RESULTS: Overall, there was no significant IL-6 trajectory differences between CBT-I and the active control (p = .64). Compared to the active control, CBT-I demonstrated greater improvement in sleep maintenance disturbance at mid-treatment (p = .01), which, in turn, was significantly associated with lower levels of IL-6 at 3-month follow-up (p < .05). Sleep maintenance disturbance at mid-treatment did not significantly predict changes in IL-6 levels at post-treatment (p = .43) and 6-month follow-up (p = .90). CONCLUSIONS: Our study demonstrates that CBT-I can be efficacious in improving sleep maintenance disturbance among individuals with knee osteoarthritis and insomnia disorder. However, no convincing evidence was found that CBT-I can substantially reduce IL-6 levels via improvement in sleep. CBT-I alone may not be effective in reducing systematic inflammation in this clinical population. TRIAL REGISTRATION: NCT00592449.

Randomized controlled trial of zolpidem as a pharmacotherapy for cannabis use disorder.

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and people who use cannabis frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates. METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing. RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives. CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

Change in Pain During Physical Activity Following Total Knee Arthroplasty: Associations With Improved Physical Function and Decreased Situational Pain Catastrophizing.

Background and Objectives: Knee osteoarthritis is one of the primary causes of chronic pain among older adults and because of the aging population, the number of total knee arthroplasties (TKAs) performed is exponentially increasing. While pain reduction is a goal of TKA, movement-evoked pain is rarely assessed pre- and post-TKA. We characterized the distributions of change in pain, function, and situational catastrophizing in patients from presurgery to 3 months postsurgery and explored associations among these pre-post changes. Research Design and Methods: This prospective study longitudinally assessed movement-evoked pain, function, and situational catastrophizing in patients with knee osteoarthritis (N = 92) using in-person performance-based tests (6-min walk test [6MWT], stair-climb test [SCT]) prior to and 3 months after TKA. Patients also completed the Western Ontario McMaster Universities Scales (WOMAC) pain and function subscales, and Pain Catastrophizing Scale, presurgery and 3- and 6-months postsurgery. Results: Movement-evoked pain and function on performance tests significantly improved from pre- to post-TKA. Improved SCT function was associated with reduced SCT pain and catastrophizing. Similarly, reduced pain during the SCT was associated with reduced catastrophizing during the SCT. However, 6MWT function was not associated with 6MWT pain or catastrophizing; yet reduced pain during the 6MWT was associated with reduced catastrophizing during the 6MWT. Reduced movement-evoked pain during both performance tests was consistently associated with improved WOMAC function and pain, whereas improved function on performance tests was inconsistently associated with WOMAC function and pain. Notably, greater movement-evoked pain on both performance tests at 3-month post-TKA was associated with worse WOMAC function and pain at 6 months, whereas better function on performance tests at 3 months was associated with better WOMAC function, but not related to WOMAC pain at 6 months. Discussion and Implications: Findings highlight the importance of situation-specific and in vivo assessments of pain and catastrophizing during physical activity.

People with IBD evidence more microarousals during sleep architecture assessments.

OBJECTIVE: Poor sleep is common in inflammatory bowel disease (IBD) and may be associated with overall worse disease outcomes. While the sleep/IBD literature is growing, the data are often self-reported. Further, much of the research using objective measures of sleep architecture, or the overall pattern of sleep depth, rely on single-night assessments, which can be of questionable validity. DESIGN: Participants with IBD and healthy controls were recruited from Dartmouth-Hitchcock Medical Center as part of a two-phase clinical trial. Sleep architecture was assessed using three nights of in-home electroencephalographic monitoring and scored according to the American Academy of Sleep Medicine guidelines. RESULTS: Our sample included 15 participants with IBD and 8 healthy controls. Participants with IBD were more psychiatrically complex, with more self-reported insomnia, anxiety and depression. Participants with IBD evidenced greater microarousals than healthy controls. In participants with IBD, microarousals were associated with lower insomnia and greater depression scores. Within IBD, participants with clinically significant insomnia evidenced trend towards lower sleep efficiency, while self-reported disease activity did not significantly impact findings. CONCLUSIONS: The methodology of past research may have impacted findings, including the reliance on single-night assessments and limited generalisability. Future research that uses robust, multinight assessments of sleep architecture in large, diverse samples is clearly warranted, as is research exploring the impact of cognitive and behavioural factors on sleep architecture and arousal. TRIAL REGISTRATION NUMBER: NCT04132024.

Presurgical sleep and pain behaviors predict insomnia symptoms and pain after total knee arthroplasty: a 12-month longitudinal, observational study.

OBJECTIVE: Up to 40% of individuals who undergo total knee arthroplasty (TKA) experience some degree of pain following surgery. Presurgical insomnia has been identified as a predictor of postsurgical pain; however, modifiable presurgical behaviors related to insomnia have received minimal attention. The objective of the present study was to develop a 2-item sleep and pain behavior scale (SP2) to investigate a maladaptive sleep and pain behavior and is a secondary analysis of a larger, parent study. METHODS: Patients (N = 109) completed SP2 at baseline and 12 months and questionnaires assessing sleep and pain at baseline (pre-TKA), 6 weeks, 3, 6, and 12 months post-TKA. SP2 demonstrated adequate preliminary psychometric properties. RESULTS: As hypothesized, even after controlling for baseline insomnia, pain, anxiety and other covariates, baseline SP2 predicted insomnia symptom severity at 6 weeks (ß = 2.828), 3 (ß = 2.140), 6 (ß = 2.962), and 12 months (ß = 1.835) and pain at 6 weeks (ß = 6.722), 3 (ß = 5.536), and 6 months (ß = 7.677) post-TKA (P < .05). Insomnia symptoms at 6-weeks post-TKA mediated the effect of presurgical SP2 on pain at 3 (95% CI: 0.024-7.054), 6 (95%CI: 0.495-5.243), and 12 months (95% CI: 0.077-2.684). CONCLUSIONS: This provides preliminary evidence that patients who cope with pain by retiring to their bed and bedroom have higher rates of post-surgical insomnia and pain and supports efforts to target this maladaptive sleep and pain behavior to reduce postsurgical pain.

Heat of the night: sleep disturbance activates inflammatory mechanisms and induces pain in rheumatoid arthritis.

Sleep has a homeostatic role in the regulation of the immune system and serves to constrain activation of inflammatory signalling and expression of cellular inflammation. In patients with rheumatoid arthritis (RA), a misaligned inflammatory profile induces a dysregulation of sleep-wake activity, which leads to excessive inflammation and the induction of increased sensitivity to pain. Given that multiple biological mechanisms contribute to sleep disturbances (such as insomnia), and that the central nervous system communicates with the innate immune system via neuroendocrine and neural effector pathways, potential exists to develop prevention opportunities to mitigate the risk of insomnia in RA. Furthermore, understanding these risk mechanisms might inform additional insomnia treatment strategies directed towards steering and reducing the magnitude of the inflammatory response, which together could influence outcomes of pain and disease activity in RA.

Association Between Insomnia and Mental Health and Neurocognitive Outcomes Following Traumatic Brain Injury.

We previously described five trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following traumatic brain injury [TBI]). Our objective in the present study was to estimate the association between insomnia trajectory status and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. In this study, participants included N = 2022 adults from the Federal Inter-agency Traumatic Brain Injury Repository database and Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. The following outcome measures were assessed serially at 2 weeks, and 3, 6, and 12 months post-injury: Insomnia Severity Index, Patient Health Questionnaire, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Patient Reported Outcomes Measurement Information System-Pain, and Quality of Life After Brain Injury-Overall Scale. Neurocognitive performance was assessed at 2 weeks, and 6 and 12 months using the Wechsler Adult Intelligence Scales Processing Speed Index and the Trails Making Test Parts A and B. Results indicated that greater insomnia severity was associated with greater abnormality in mental health, quality of life, and neuropsychological testing outcomes. The pattern of insomnia over time tracked the temporal pattern of all these outcomes for all but a very small number of participants. Notably, severe insomnia at 3 or 6 months post-TBI was a risk factor for poor recovery at 12 months post-injury. In conclusion, in this well-characterized sample of individuals with TBI, insomnia severity generally tracked severity of depression, pain, PTSD, quality of life, and neurocognitive outcomes over 12 months post-injury. More intensive sleep assessment is needed to elucidate the nature of these relationships and to help inform best strategies for intervention.

Perioperative insomnia trajectories and functional outcomes after total knee arthroplasty.

ABSTRACT: Longitudinal total knee arthroplasty (TKA) studies indicate that a substantial percentage of patients continue to experience clinically significant pain and functional impairment after surgery. Insomnia has been associated with poorer surgical outcomes; however, previous work has largely focused on long-term postsurgical insomnia. This study builds on previous work by examining sleep and pain outcomes about perioperative insomnia trajectories. Insomnia symptoms (using the Insomnia Severity Index) during the acute perioperative period (2 weeks pre-TKA to 6 weeks post-TKA) were used to classify participants into perioperative insomnia trajectories: (1) No Insomnia (ISI < 8), (2) New Insomnia (baseline < 8; postoperative ≥ 8 or ≥6-point increase), (3) Improved Insomnia (baseline ≥ 8, postoperative < 8 or ≥6-point decrease), and (4) Persistent Insomnia (ISI ≥ 8). Insomnia, pain, and physical functioning were assessed in participants with knee osteoarthritis (n = 173; M age = 65 ± 8.3, 57.8% female) at 5 time points: 2 weeks pre-TKA, post-TKA: 6 weeks, 3 months, 6 months, and 12 months. Significant main effects were seen for insomnia trajectory and time, and trajectory-by-time interactions for postoperative insomnia, pain severity, and physical functioning ( P' s < 0.05). The Persistent Insomnia trajectory had the worst postoperative pain at all follow-ups and marked insomnia and physical functioning impairment post-TKA ( P' s < 0.05). The New Insomnia trajectory had notable long-term insomnia (6 weeks to 6 months) and acute (6 weeks) postoperative pain and physical functioning ( P' s < 0.05). Findings indicated a significant relationship between perioperative insomnia trajectory and postoperative outcomes. Results of this study suggest that targeting presurgical insomnia and preventing the development of acute postoperative insomnia may improve long-term postoperative outcomes, with an emphasis on persistent perioperative insomnia due to poorer associated outcomes.

A randomized, placebo-controlled, double-blinded mechanistic clinical trial using endotoxin to evaluate the relationship between insomnia, inflammation, and affective disturbance on pain in older adults: A protocol for the sleep and Healthy Aging Research for pain (SHARE-P) study.

Chronic pain is prevalent in older adults. Treatment, especially with opioids, is often ineffective and poses considerable negative consequences in this population. To improve treatment, it is important to understand why older adults are at a heightened risk for developing chronic pain. Insomnia is a major modifiable risk factor for chronic pain that is ubiquitous among older adults. Insomnia can also lead to heightened systemic inflammation and affective disturbance, both of which may further exacerbate pain conditions in older adults. Endotoxin exposure can be used as an experimental model of systemic inflammation and affective disturbance. The current study aims to understand how insomnia status and endotoxin-induced changes in inflammation and affect (increased negative affect and decreased positive affect) may interact to impact pain facilitatory and inhibitory processes in older adults. Longitudinal data will also assess how pain processing, affective, and inflammatory responses to endotoxin may predict the development of pain and/or depressive symptoms. The current study is a randomized, double-blinded, placebo-controlled, mechanistic clinical trial in men and women, with and without insomnia, aged 50 years and older. Participants were randomized to either 0.8ng/kg endotoxin injection or saline placebo injection. Daily diaries were used to collect variables related to sleep, mood, and pain at two-week intervals during baseline and 3-, 6-, 9-, and 12-months post-injection. Primary outcomes during the experimental phase include conditioned pain modulation, temporal summation, and affective pain modulation ∼5.5 hours after injection. Primary outcomes for longitudinal assessments are self-reported pain intensity and depressive symptoms. The current study uses endotoxin as an experimental model for pain. In doing so, it aims to extend the current literature by: (1) including older adults, (2) investigating insomnia as a potential risk factor for chronic pain, (3) evaluating the role of endotoxin-induced affective disturbances on pain sensitivity, and (4) assessing sex differences in endotoxin-induced hyperalgesia. Clinicaltrialsgov: NCT03256760. Trial sponsor: NIH R01AG057750-01.

Patients with IBD Want to Talk About Sleep and Treatments for Insomnia with Their Gastroenterologist.

BACKGROUND AND AIMS: Poor sleep may be prospectively associated with worse disease course in inflammatory bowel disease (IBD). Chronic insomnia is the most common cause of poor sleep complaints in IBD and is theorized to be maintained by dysfunctional thoughts and behavioral patterns. However, data characterizing patterns specific to insomnia in IBD are lacking. Understanding the nuances of insomnia and patients' preferences for treatment is critical for addressing this significant comorbidity in IBD. METHODS: We conducted an anonymous, mixed-method online survey of people with IBD and asked questions about sleep patterns, thoughts, and behaviors related to sleep, treatment preferences, and barriers to treatment. RESULTS: 312 participants (60.9% Crohn's, 66.3% women, mean age of 48.62 years) were included in this study. Participants with insomnia were significantly more concerned about the consequences of sleep loss, felt more helpless about their sleep, and were more likely to engage in behaviors known to perpetuate insomnia (e.g., spending time in bed in pain; ps ≤ 0.001) than those without insomnia. 70.3% of participants were interested in discussing sleep as part of IBD care, 63.5% were interested in receiving sleep recommendations from their gastroenterologist, and 84.6% of those with insomnia were interested in participating in sleep treatments. CONCLUSION: Participants with IBD and insomnia are interested in treatment and reported patterns that can be targeted in Cognitive Behavioral Therapy for Insomnia, as opposed to traditional sleep hygiene guidelines. Additionally, people with insomnia engaged in several sleep-interfering behaviors related to pain. Clinical trials that target insomnia in people with IBD should include pain management in the intervention.

Depressive and Insomnia Symptoms Sequentially Mediate the Association Between Racism-Based Discrimination in Healthcare Settings and Clinical Pain Among Adults With Sickle Cell Disease.

Racism-based discrimination in healthcare settings has been associated with clinical pain in adults living with sickle cell disease; however, no studies have examined depressive and insomnia symptoms as mechanisms that may drive this relationship. This secondary data analysis examined associations between depressive and insomnia symptoms, racism-based discrimination, and clinical pain. Seventy-one adults with sickle cell disease (70% female, Mage = 38.79) provided baseline reports of racism-based discrimination, depressive symptoms, insomnia symptoms, and pain (severity, interference, catastrophizing), and they completed daily diaries of pain severity and interference over 3 months. In a sequential mediation model, baseline depressive (1st) and insomnia symptoms (2nd) significantly mediated the association between racism-based discrimination and baseline pain interference, average daily diary pain severity, and average daily diary pain interference. Although the mediation model with baseline pain severity as the outcome was significant, the total and direct effects were not. Results indicate that discrimination in healthcare settings contributes to depression, which may act on pain through sleep disturbance. Findings support the need for systemic and structural changes to eliminate discrimination in healthcare settings and behavioral mood and sleep interventions to reduce the impact of discrimination on clinical pain. PERSPECTIVE: The relationship between discrimination in healthcare settings and pain in adults with sickle cell disease may be driven by depression and sleep disturbance, modifiable risk factors and potential treatment targets. Results suggest that systemic, structural, and institutional changes must be implemented to promote better patient care and health outcomes.

Nocturnal Delta Power is Associated With Lower Next-Day Pain But Not Pain Catastrophizing: Results From a Cohort of Female Participants With Temporomandibular Joint Pain.

Existing data demonstrate reduced delta power during sleep in patients with depression and chronic pain. However, there has been little examination of the relationship between delta power and pain-reports, or pain-catastrophizing. We recruited female participants (n = 111) with insomnia and temporomandibular disorder, and measured nocturnal and daytime measures of pain and pain catastrophizing, and calculated relative nocturnal delta (0.5-4 Hz) power during sleep. We fit linear regression models, and further examined the moderating effect of depressive symptom severity. Lower relative delta power across the whole night was significantly associated with greater nocturnal pain (B = -20.276, P = .025, R2 = 0.214). Lower relative delta power during the first-third of the night, was associated with greater nocturnal pain (B = -17.807, p = 0.019, R2 = 0.217), next-day pain (B = 13.876, P = .039, R2 = 0.195), and next-morning pain (B = -15.751, P = .022, R2 = 0.198). Lower relative delta power during the final-third of the night was significantly associated with greater nocturnal (B = -17.602, P = .029, R2 = 0.207) and next-morning pain (3rd: B = -14.943, P = .042, R2 = 0.187). Depressive symptom severity did not moderate these relationships. Delta power was not significantly associated with nocturnal or daytime pain catastrophizing. These findings demonstrate that greater relative delta power during sleep is associated with lower nocturnal and next-day pain in patients with temporomandibular disorder. This data may guide the use of sleep interventions in clinical pain populations, with the aim of improving pain outcomes. PERSPECTIVE: This article presents data demonstrating an association between increased nocturnal delta power and reduced next-day pain. These findings may help promote interventions which aim to increase nocturnal delta power in clinical pain populations, with the goal of improving pain outcomes.

Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial.

ABSTRACT: Sleep loss heightens pain sensitivity, but the pathways underlying this association are not known. Given that experimental sleep disruption induces increases in cellular inflammation as well as selective loss of slow wave, N3 sleep, this study examined whether these mechanisms contribute to pain sensitivity following sleep loss in healthy adults. This assessor-blinded, cross-over sleep condition, single-site, randomized clinical trial enrolled 95 healthy adults (mean [SD] age, 27.8 [6.4]; female, 44 [53.7%]). The 2 sleep conditions were 2 nights of undisturbed sleep (US) and 2 nights of sleep disruption or forced awakening (FA, 8 pseudorandomly distributed awakenings and 200 minutes wake time during the 8-hour sleep opportunity), administered in a cross-over design after 2 weeks of washout and in a random order (FA-US; US-FA). Primary outcome was heat pain threshold (hPTH). Sleep architecture was assessed by polysomnography, and morning levels of cellular inflammation were evaluated by Toll-like receptor-4 stimulated monocyte intracellular proinflammatory cytokine production. As compared with US, FA was associated with decreases in the amount of slow wave or N3 sleep ( P < 0.001), increases in Toll-like receptor-4 stimulated production of interleukin-6 and tumor necrosis factor-α ( P = 0.03), and decreases in hPTH ( P = 0.02). A comprehensive causal mediation analysis found that FA had an indirect effect on hPTH by decreases in N3 sleep and subsequent increases in inflammation (estimate=-0.15; 95% confidence interval, -0.30 to -0.03; P < 0.05) with the proportion mediated 34.9%. Differential loss of slow wave, N3 sleep, and increases in cellular inflammation are important drivers of pain sensitivity after sleep disruption.Clinical Trials Registration: NCT01794689.

Brief Mindfulness-Based Cognitive Behavioral Therapy is Associated with Faster Recovery in Patients Undergoing Total Knee Arthroplasty: A Pilot Clinical Trial.

OBJECTIVE: To assess whether brief mindfulness-based cognitive behavioral therapy (MBCBT) could enhance the benefits of total knee arthroplasty (TKA) in improving pain and pain-related disability. Specifically, to determine 1) whether patients who received MBCBT differed from matched controls who received treatment-as-usual with regard to postsurgical pain outcomes and 2) whether changes in pain catastrophizing, depression, or anxiety explained the potential effects of MBCBT on pain outcomes. DESIGN: Pilot clinical trial. SETTING: An academic teaching hospital serving a large urban and suburban catchment area surrounding the Boston, Massachusetts metropolitan region. SUBJECTS: Sample of 44 patients undergoing TKA. Patients who completed a brief MBCBT intervention (n = 22) were compared with age-, race-, and sex-matched controls who received treatment-as-usual (n = 22). METHODS: The MBCBT intervention included four 60-minute sessions delivered by a pain psychologist in person and via telephone during the perioperative period. Participants were assessed at baseline and at 6 weeks, 3 months, and 6 months after surgery. RESULTS: Compared with matched controls, patients who received MBCBT had lower pain severity and pain interference at 6 weeks after surgery. Group differences in outcomes were mediated by changes in pain catastrophizing but not by changes in depression or anxiety. The MBCBT group had similar reductions in pain severity and interference as the control group did at 3 and 6 months after surgery. CONCLUSIONS: This work offers evidence for a safe and flexibly delivered nonpharmacological treatment (MBCBT) to promote faster recovery from TKA and identifies change in pain catastrophizing as a mechanism by which this intervention could lead to enhanced pain-related outcomes.

Adverse childhood experiences and sleep links in a predominantly Black sample of overweight adults.

Adverse childhood experiences (ACEs) have been associated with worse sleep, but existing literature is limited by use of predominantly White samples, lack of objective sleep measurement, and use of non-standardized questionnaires. We investigated associations between retrospectively reported ACEs and sleep in adulthood in a sample of 43 adults 20-53 years of age, free from chronic conditions, with a Body mass index (BMI) ≥ 25 (Mean age = 33.14 [SD = 10.05], 74% female, 54% Black). Sleep efficiency (SE), total sleep time (TST), wake after sleep onset (WASO), and sleep onset latency (SOL), were measured by actigraphy and daily diary. Global sleep quality and insomnia severity were measured by questionnaires. Sleepiness, fatigue, and sleep quality were also measured by daily diary. Adjusting for demographic characteristics and BMI, ACEs were significantly associated with poorer global sleep quality and diary measures of greater daytime sleepiness, fatigue, and poorer sleep quality. There were no significant associations between ACEs and SE, TST, WASO, or SOL measured by diary or actigraphy. Findings suggest that ACEs are associated with worse sleep perception and daytime functioning in adulthood. Larger prospective studies are needed to replicate these findings, examine racial/ethnic differences, and determine temporal associations between ACEs, sleep, and health (e.g., BMI).

Preliminary Evidence for the Sequentially Mediated Effect of Racism-Related Stress on Pain Sensitivity Through Sleep Disturbance and Corticolimbic Opioid Receptor Function.

Sleep disturbance predicts worse pain outcomes. Because sleep disturbance inequitably impacts Black adults - with racism as the upstream cause - understanding how racism-related stress impacts pain through sleep might help minimize racialized pain inequities. This preliminary study examined sequential mediation of the effect of racism-related stress on experimental pain through sleep disturbance and corticolimbic µOR function in pain-free non-Hispanic Black (NHB) and White (NHW) adults. Participants completed questionnaires, actigraphy, positron emission tomography, and sensory testing. We reproduced findings showing greater sleep disturbance and pain sensitivity among NHB participants; greater sleep disturbance (r = .35) and lower pain tolerance (r=-.37) were significantly associated with greater racism-related stress. In a sequential mediation model, the total effect of racism-related stress on pain tolerance (ß=-.38, P = .005) weakened after adding sleep disturbance and ventromedial prefrontal cortex (vmPFC) µOR binding potential (BPND) as mediators (ß = -.18, P = .16). The indirect effect was statistically significant [point estimate = -.003, (-.007, -.0003). Findings showed a potential sequentially mediated effect of racism-related stress on pain sensitivity through sleep disturbance and vmPFC µOR BPND. As policy efforts are enacted to eliminate the upstream cause of systemic racism, these results cautiously suggest that sleep interventions within racism-based trauma informed therapy might help prevent downstream effects on pain. PERSPECTIVE: This preliminary study identified the effect of racism-related stress on pain through sleep disturbance and mu-opioid receptor binding potential in the ventromedial prefrontal cortex. Findings cautiously support the application of sleep interventions within racism-based trauma-informed therapy to prevent pain inequities as policy changes function to eliminate all levels of racism.

A comparison of cognitive behavioral therapy for insomnia to standard of care in an outpatient substance use disorder clinic embedded within a therapeutic community: a RE-AIM framework evaluation.

BACKGROUND: Rates of substance use disorders (SUDs) continue to rise in the USA with parallel rises in admissions to outpatient SUD treatment programs. Insomnia symptoms reduce treatment adherence, trigger relapse, and generally undermine SUD recovery efforts. Cognitive-behavioral therapy for insomnia (CBT-I) is the first-line treatment recommended for chronic insomnia. No study has examined the effectiveness of CBT-I for individuals who recently entered an outpatient SUD treatment program embedded within a therapeutic community (i.e., long-term drug-free residential setting). METHODS: A randomized controlled trial conducted at a SUD program embedded in a therapeutic community aimed to compare group-based CBT-I (gCBT-I) (N = 10) with the standard of care (SOC) (N = 11) among individuals who have SUDs and comorbid insomnia. We present a RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework evaluation to provide empirical data on gCBT-I feasibility and facilitators and barriers of conducting an insomnia-focused clinical effectiveness study within a therapeutic community. RESULTS: Participants in both study arms reported moderately severe insomnia symptoms at admission and reductions in insomnia symptoms over time. Among participants who completed the Insomnia Severity Index (ISI) beyond admission, ISI decreased to ≤ 8 (the clinical cutoff for mild insomnia) in 80% of individuals in the gCBT-I group compared with 25% of individuals in the SOC group. A RE-AIM framework evaluation showed initial success with Reach and Adoption while Implementation, and Maintenance were limited. Effectiveness was inconclusive because of challenges with recruitment, intervention integrity, and missing data that precluded meeting the planned recruitment and study aims and led to study termination. Coordination and communication with staff and leadership facilitated gCBT-I implementation, yet well-known CBT-I barriers including time- and resource-intensive sleep medicine training for interventionalists and maintenance of treatment integrity during an 8-week intervention limited gCBT-I sustainability. CONCLUSIONS: This analysis supports the feasibility of conducting behavioral sleep medicine research in outpatient SUD treatment programs embedded within therapeutic communities. Implementation of an insomnia-focused intervention was widely accepted by patients and providers and has potential to address insomnia symptoms in early SUD recovery. Addressing patient- and organizational-level implementation barriers may enhance the sustainability and scalability of sleep interventions and provide new hope to effectively treat insomnia among people living with SUDs. TRIAL REGISTRATION: Clinicaltrials.gov : NCT03208855. Registered July 6, 2017https://clinicaltrials.gov/ct2/show/NCT03208855?term=NCT03208855&draw=2&rank=1.