Sleep and Pain in Veterans with Chronic Pain: Effects of Psychological Pain Treatment and Temporal Associations.

Introduction: Chronic pain is highly prevalent in US military Veterans. Non-opioid and non-pharmacologic treatments are recommended when clinically appropriate, but research on the mechanisms underlying benefits of these treatments is lacking. Here, we examined the role of sleep in the effects of three non-pharmacologic pain treatments in Veterans. Specifically, we investigated whether treatment effects on sleep predicted treatment effects on pain occurring later, or vice versa. Methods: Veterans enrolled in a randomized controlled trial were invited to participate in this supplementary sleep study. A total of 174 Veterans were randomized to one of three 8-session, in-person, group-based pain treatments: hypnosis, mindfulness meditation, or education control. Measurements included self-reported sleep disturbance, pain intensity, and pain catastrophizing; sleep duration was assessed with actigraphy. Sleep and pain measurements were obtained at baseline, posttreatment, and 3-month posttreatment follow-up. Results: At baseline, average pain intensity was moderate (mean ± SD: 5.7 ± 1.7 on the 0-10 Numeric Rating Scale), pain catastrophizing was just below the clinically relevant threshold (mean ± SD: 28.6 ± 12.2 on the Pain Catastrophizing Scale), and subjective sleep disturbance exceeded the US population average (mean ± SD: 58.5 ± 8.1 on the Patient Reported Outcomes Measurement Information System Sleep Disturbance - Short Form). By contrast, objective sleep duration was consistent with the recommended daily sleep amount of 7-8 h for adults (mean ± SD: 8.3 ± 1.4 h). Across treatment conditions, pain intensity, pain catastrophizing, and subjective sleep disturbance were significantly less at posttreatment and 3-month follow-up than at baseline (p < 0.001). Actigraphic sleep duration did not differ significantly as a function of time. There was a high degree of covariation among the measures of pain intensity, pain catastrophizing, and sleep disturbance (p < 0.05). However, self-reported sleep disturbance was not significantly correlated with actigraphic sleep duration (|r| <= 0.13, p > 0.05). Sleep and pain variables observed at prior assessments predicted these same variables at subsequent assessments. There was no significant evidence that changes in pain preceded changes in sleep or that changes in sleep preceded changes in pain (all p > 0.05). Discussion: For this study's Veterans, treatment-related changes in sleep and pain appeared to occur in parallel. The concomitant changes in sleep and pain suggest that therapies improving pain in Veterans may yield attendant benefits for the treatment of sleep, and possibly vice versa.

Nighttime Sleep and Respiratory Disturbances in Individuals Receiving Methadone to Treat Opioid Use Disorder.

ABSTRACT: Opioids are a leading cause of drug overdose deaths in the United States. Methadone used as medication for opioid use disorder (MOUD) reduces drug cravings and promotes abstinence. However, individuals in methadone-based MOUD treatment commonly report subjective sleep complaints and are at risk for respiratory depression from opioids. We investigated nighttime sleep and respiratory function in eight individuals (six women, two men; ages 31-68 years) in their first 90 days of methadone-based MOUD treatment. Participants underwent overnight cardiorespiratory polysomnography. Sleep and respiratory variables were characterized with descriptive statistics for comparison to reference data from similarly aged healthy adults. Although participants spent 8.1 ± 0.3 hours (mean ± SD ) in bed, their total sleep time was only 6.8 ± 1.3 hours. They exhibited longer sleep latency and intermittent wakefulness. Sleep structure was irregular, with disrupted sleep cycles. Participants also displayed a decreased amount of N1 sleep and an increased amount of N3 sleep, compared with reference data. Participants showed respiratory depression, with an average apnea-hypopnea index of 16.5 ± 8.9 events per hour. Central sleep apneas comprised 69.1% ± 20.9% of the respiratory events. A Cheyne-Stokes-like breathing pattern, consisting of 30-second cycles of three central sleep apneas, was observed in 75% of participants. Our results suggest that individuals early in methadone-based MOUD treatment experience disordered sleep and respiratory disturbances. Such nighttime physiological changes may have serious long-term health consequences and contribute to unintended overdose rates. Identifying and treating MOUD individuals with sleep apnea could reduce risk of death.

Effects of total sleep deprivation on components of top-down attentional control using a flexible attentional control task.

Sleep deprivation consistently decreases vigilant attention, which can lead to difficulty in performing a variety of cognitive tasks. However, sleep-deprived individuals may be able to compensate for degraded vigilant attention by means of top-down attentional control. We employed a novel task to measure the degree to which individuals overcome impairments in vigilant attention by using top-down attentional control, the Flexible Attentional Control Task (FACT). The FACT is a two-choice task that has trials with valid, invalid, and neutral cues, along with an unexpected switch in the probability of cue validity about halfway in the task. The task provides indices that isolate performance components reflecting vigilant attention and top-down attentional control. Twelve healthy young adults completed an in-laboratory study. After a baseline day, the subjects underwent 39 hours of total sleep deprivation (TSD), followed by a recovery day. The FACT was administered at 03:00, 11:00, and 19:00 during sleep deprivation (TSD condition) and at 11:00 and 19:00 after baseline sleep and at 11:00 after recovery sleep (rested condition). When rested, the subjects demonstrated both facilitation and interference effects on cued trials. While sleep deprived, the subjects showed vigilant attention deficits on neutral cue trials, and an impaired ability to reduce these deficits by using predictive contextual cues. Our results indicate that the FACT can dissociate vigilant attention from top-down attentional control. Furthermore, they show that during sleep deprivation, contextual cues help individuals to compensate partially for impairments in vigilant attention, but the effectiveness of top-down attentional control is diminished.

Drug-Drug Interaction Between Orally Administered Hydrocodone-Acetaminophen and Inhalation of Cannabis Smoke: A Case Report.

Objective: To determine if a 2-day protocol measuring pharmacokinetic and pharmacodynamic characteristics can demonstrate drug-drug interactions when smoked cannabis is added to orally administered hydrocodone/acetaminophen combination products. Case Summary: A 51-year-old non-Hispanic white male with chronic pain diagnoses participated in a 2-day pilot protocol. The participant attended two 7-hour in-lab days where he received 10 blood draws each day and completed self-administered pain and anxiety surveys. For both days, the participant took his prescribed dose of hydrocodone/acetaminophen (1/2 tablet of 7.5 mg/325 mg combination product) with the addition of 1 smoked pre-rolled marijuana cigarette (labeled as 0.5 g; 22.17% Δ9-tetrahydrocannabinol; 0.12% cannabidiol) on Day 2. Blood specimens were analyzed using mass spectrometry to quantify the difference of plasma hydrocodone levels between Day 1 and Day 2. Results: Compared to Day 1, lower levels of pain and anxiety were reported during Day 2 with the addition of cannabis to oral hydrocodone/acetaminophen. Day 2 pharmacokinetic analysis also revealed more rapid absorption and overall lower levels of hydrocodone in plasma. Discussion: Lower hydrocodone plasma levels in Day 2 may indicate cannabis's effect on metabolism and reduce the risk of opioid toxicity. The quicker absorption rate of hydrocodone could explain lower pain and anxiety scores reported on the second day. Conclusion and Relevance: A 2-day protocol was able to capture differences across time in pharmacokinetic and pharmacodynamic measurements. Larger studies can be designed to better characterize the potential drug-drug interaction of cannabis and opioids.

Pain Catastrophizing Mediates the Relationship Between Pain Intensity and Sleep Disturbances in U.S. Veterans With Chronic Pain.

INTRODUCTION: Veterans with chronic pain frequently report comorbid disruptions in sleep and psychological dysfunction. The purpose of this study was to investigate whether psychological function variables mediate the sleep-pain relationship. Knowledge regarding such contributing factors can inform the development and optimization of treatments for sleep disturbances and pain. MATERIALS AND METHODS: In an IRB-approved, registered clinical trial, we collected objective sleep data from U.S. military Veterans with chronic pain (N = 184, ages 23-81) using wrist actigraphy for 7 days and self-reported survey data assessing sleep quality, pain intensity, and psychological function (depression, anxiety, post-traumatic stress disorder, and pain catastrophizing). We investigated the associations between objectively measured and self-reported sleep quality and self-reported pain intensity. In addition, using parallel mediation analyses, we examined whether psychological function variables mediated these associations. RESULTS: Actigraphy showed suboptimal sleep duration (less than 7 hours) and sleep fragmentation for most participants. Self-reported poor sleep quality and pain intensity were significantly correlated. Pain catastrophizing was found to mediate the association between self-reported sleep quality and pain intensity. CONCLUSIONS: Sleep disturbances in this sample of Veterans with chronic pain included insufficient sleep, fragmented sleep, and perceived poor sleep quality. Analyses suggest that poor perceived sleep quality and pain intensity are mediated via pain catastrophizing. The finding highlights the potential importance of pain catastrophizing in Veterans with chronic pain. Future longitudinal research is needed to determine the extent to which treatments that reduce pain catastrophizing might also improve both sleep and pain outcomes.

Trait Interindividual Differences in the Magnitude of Subjective Sleepiness from Sleep Inertia.

In shift work settings and on-call operations, workers may be at risk of sleep inertia when called to action immediately after awakening from sleep. However, individuals may differ substantially in their susceptibility to sleep inertia. We investigated this using data from a laboratory study in which 20 healthy young adults were each exposed to 36 h of total sleep deprivation, preceded by a baseline sleep period and followed by a recovery sleep period, on three separate occasions. In the week prior to each laboratory session and on the corresponding baseline night in the laboratory, participants either extended their sleep period to 12 h/day or restricted it to 6 h/day. During periods of wakefulness in the laboratory, starting right after scheduled awakening, participants completed neurobehavioral tests every 2 h. Testing included the Karolinska Sleepiness Scale to measure subjective sleepiness, for which the data were analyzed with nonlinear mixed-effects regression to quantify sleep inertia. This revealed considerable interindividual differences in the magnitude of sleep inertia, which were highly stable within individuals after both baseline and recovery sleep periods, regardless of study condition. Our results demonstrate that interindividual differences in subjective sleepiness due to sleep inertia are substantial and constitute a trait.

Self-Reported Sleep Need, Subjective Resilience, and Cognitive Performance Following Sleep Loss and Recovery Sleep.

OBJECTIVE: Individuals vary in response to sleep loss: some individuals are "vulnerable" and demonstrate cognitive decrements following insufficient sleep, while others are "resistant" and maintain baseline cognitive capability. Physiological markers (e.g., genetic polymorphisms) have been identified that can predict relative vulnerability. However, a quick, cost-effective, and feasible subjective predictor tool has not been developed. The objective of the present study was to determine whether two factors-"subjective sleep need" and "subjective resilience"-predict cognitive performance following sleep deprivation. METHODS: Twenty-seven healthy, sleep-satiated young adults participated. These individuals were screened for sleep disorders, comorbidities, and erratic sleep schedules. Prior to 40 hours of in-laboratory total sleep deprivation, participants were questioned on their subjective sleep need and completed a validated resilience scale. During and after sleep deprivation, participants completed a 5-minute psychomotor vigilance test every 2 hours. RESULTS: Both subjective resilience and subjective sleep need individually failed to predict performance during sleep loss. However, these two measures interacted to predict performance. Individuals with low resilience and low sleep need had poorer cognitive performance during sleep loss. However, in individuals with medium or high resilience, psychomotor vigilance test performance was not predicted by subjective sleep need. Higher resilience may be protective against sleep loss-related neurobehavioral impairments in the context of subjective sleep need. CONCLUSIONS: Following sleep loss (and recovery sleep), trait resilient individuals may outperform those with lower resiliency on real-world tasks that require continuous attention. Future studies should determine whether the present findings generalize to other, operationally relevant tasks and additional cognitive domains.

Robustness of inter-individual differences in slow wave sleep for daytime sleep periods after total sleep deprivation with or without caffeine administration: potential implications for around-the-clock operations.

There are large inter-individual differences in slow wave sleep, which constitute a trait or phenotype. We investigated whether the manifestation of this trait is impacted by daytime sleeping after sleep deprivation, and to what extent it is robust to prior caffeine intake. N = 12 subjects underwent three 48 h periods of total sleep deprivation with different caffeine dosing regimens. There were significant, considerable, and robust inter-individual differences in slow wave sleep across nighttime sleep opportunities before, and daytime sleep after, total sleep deprivation, regardless of caffeine dosing. The robustness of this phenotype may have functional implications for individuals in around-the-clock operational settings.

TNFα G308A genotype, resilience to sleep deprivation, and the effect of caffeine on psychomotor vigilance performance in a randomized, double-blind, placebo-controlled, crossover study.

The TNFα G308A gene polymorphism has been reported to influence performance impairment during total sleep deprivation (TSD). We investigated this effect in a randomized, double-blind, crossover laboratory study of repeated exposure to 48 h TSD with caffeine administration at different doses. In a retrospective analysis, we replicated the finding that the A allele of TNFα G308A, found in 4 of 12 study participants, confers resilience to performance impairment during TSD. There was no evidence of an interaction of TNFα genotype with the beneficial effect of caffeine (200 or 300 mg) on performance during TSD, suggesting distinct underlying mechanisms.

Examination of Sleep and Injury Among College Football Athletes.

Burke, TM, Lisman, PJ, Maguire, K, Skeiky, L, Choynowski, JJ, CapaldiII, VF, Wilder, JN, Brager, AJ, and Dobrosielski, DA. Examination of sleep and injury among college football athletes. J Strength Cond Res 34(3): 609-616, 2020-The purpose of this study was to characterize subjective sleep metrics in collegiate football players at the start of the season, determine the relationship between preseason subjective sleep measures and in-season objective sleep characteristics, and examine the association between subjective and objective sleep metrics and incidence of time-loss injury during the competitive season. Ninety-four Division I football players completed 5 validated sleep-related questionnaires to assess sleep quality, insomnia severity, daytime sleepiness, sleep apnea risk, and circadian preference before the start of the season. Clinical thresholds for sleep questionnaires were used to determine risk of sleep disorders. Continuous wrist actigraphy was collected throughout the season to generalize sleep behaviors. Time-loss injury incidence data were recorded and used for analysis. Results indicated that 67.4% (60 of 89) of athletes scored above clinical threshold in at least 1 questionnaire to indicate sleep disorder risk. At the start of the season, players subjectively reported an average sleep duration of 7:16 ± 1:18 hours:minutes, which was in contrast to the 6:04 ± 0:41 hours:minutes measured through actigraphy during the season. Logistic regression models adjusted for age and body mass index revealed no significant associations between injury and subjective (odds ratio [OR] = 1.00; 95% confidence interval [CI] = 0.99-1.01) and objective (OR = 1.01; 95% CI = 0.99-1.02) sleep duration or measures attained from sleep questionnaires (ORs ranged from 1.01 to 2.87). Sleep metrics (quantity and quality) were not associated with increased risk of injury in this cohort of collegiate football players.

Sleep problems and functioning during initial training for a high-risk occupation.

OBJECTIVES: The current study sought to characterize the sleep problems of soldiers entering Basic Combat Training and to identify the link between sleep problems and subsequent performance, psychological distress, anger reactions, and attention. DESIGN: Soldiers were surveyed at 4 time points throughout the standard 10 weeks of Basic Combat Training. Surveys were administered at weeks 1, 3, 6, and 9. Sleep problems were identified as either present or absent at each time point using a sleep problem screening questionnaire. Four sleep patterns were identified and then used to evaluate outcomes throughout training (n = 1577). RESULTS: When compared to those who never had a sleep problem ("healthy "; 60.6%), those who recovered from their initial sleep problem ("recovered"; 12.8%) started training with higher psychological distress and anger reactions and lower attention but steadily improved throughout training. Those who developed a sleep problem during training ("new onset"; 20.0%) and those who had a sleep problem throughout training ("chronic"; 6.6%) also started off significantly worse than the healthy group. The new-onset and chronic groups saw slower psychological distress improvement and a decline in attention throughout the course compared to the healthy group. The chronic group also significantly increased their anger reactions throughout training compared to the healthy group. CONCLUSION: Sleep problems during Basic Combat Training may be an indicator for difficulties managing entry into the military. These findings highlight the importance of improving sleep health for soldiers throughout Basic Combat Training and for others with similar training in high-risk occupations.

Objective changes in activity levels following sleep extension as measured by wrist actigraphy.

OBJECTIVE/BACKGROUND: It is widely established that insufficient sleep can lead to adverse health outcomes. Paradoxically, epidemiologic research suggests that individuals who report habitual nightly sleep greater than 9 h also are at risk for adverse health outcomes. Further, studies have shown that long sleepers have decreased activity levels, which may partially explain the relationship between long sleep duration and mortality. The influence of sleep extension (longer time in bed) on levels of daily activity has not yet been established. The current study examined whether a week of sleep extension altered activity levels within the subsequent daily waking active and sleep period in order to determine whether increased time in bed indeed is related to decreased activity levels. METHODS: A total of 26 healthy volunteers wore wrist accelerometer devices (Actiwatch 2.0, Philips) in order to objectively measure sleep and activity for six days during their normal schedules and for six days during a sleep extension (10 h time in bed) intervention. RESULTS: There were no significant or clinically-relevant differences in 24-h activity or activity during the active or sleep period between baseline and sleep extension conditions. There were no main or interaction effects of day and condition when daily activity counts were compared between baseline and sleep extension conditions for the 24 h period (Day: F(5, 21) = 1.92, p = 0.12; Condition: F(1,25) = 2.93, p = 0.09; Day by Condition: F(5,21) = 0.32, p = 0.83), Active Waking Period (Day: F(5,25) = 1.53, p = 0.18; Condition: F(1,25) = 0.26, p = 0.61; Day by Condition: F(5,21) = 0.55, p = 0.74) or Nightly Sleep (Day: F(5,21) = 0.86, p = 0.51; Condition: F(1,25) = 1.78, p = 0.19; Day by Condition: F(5,21) = 0.79, p = 0.56) periods. In contrast, there was a main effect of condition when examining sleep duration by day between conditions (Day: F(5,21) = 1.60, p = 0.16; Condition: F(1,25) = 167.31, p < 0.001; Day by Condition: F(5,21) = 2.31, p = 0.07), such that sleep duration was longer during the sleep extension condition. DISCUSSION: Sleep duration increased during six days of a sleep extension protocol but activity levels remained similar to their baseline (normal) sleep schedule. The current findings suggest that extending time in bed alone does not alter waking activity counts in young healthy adults. The link between extended sleep and adverse health outcomes may be attributable to other phenotypic factors, or other biological correlates of extended sleep and poor health.

Sleep extension reduces fatigue in healthy, normally-sleeping young adults.

OBJECTIVE: To assess the effects of one week of sleep extension on mood, fatigue and subjective sleepiness in normal-sleeping young adults. METHODS: Twenty-seven adults (age 24.4±5.4 years, 11 female) participated. At-home baseline sleep/wake patterns were recorded with wrist actigraphy for 14 days. This was followed by two nights of in-lab baseline sleep with 8 hours time in bed (TIB), then 7 nights with TIB extended to 10 hours (2100-0700 hours). Fatigue, mood, and sleepiness were assessed following the 2nd and 9th nights of in-laboratory sleep (i.e., 2 nights with 8hTIB and 7 nights with 10 hours TIB, respectively) using the Automated Neuropsychological Assessment Metric and Karolinska Sleepiness Scale. Paired t-tests were used to compare mood, fatigue, and sleepiness ratings between conditions. RESULTS: At-home wrist actigraphy revealed a mean nightly total sleep time (TST) of 7.53 +/- 0.88 hours of sleep per night. Mean in-lab baseline sleep duration (7.76 +/- 0.59) did not differ from at-home sleep. However, during sleep extension, mean TST was 9.36 +/- 0.37 hours per night, significantly more than during the in-lab baseline (p < .001). Following sleep extension, fatigue ratings were significantly reduced, relative to baseline (p = .03). However, sleep extension had no other significant effects on subjective ratings of mood or sleepiness. CONCLUSIONS: Sleep extension resulted in reduced fatigue in healthy, normal-sleeping young adults, although subjective sleepiness and mood were not improved. Implications include the possibility that (a) the effects of sleep extension on various aspects of mood depend upon the extent to which those aspects of mood are made salient by the study design and methodology; and (b) sleep extension may prove beneficial to fatigue-related conditions such as "burnout."