The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

AIMS: Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. METHODS: Participants in residential OUD treatment (n = 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. RESULTS: Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. CONCLUSIONS: Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.

Investigating psychological mechanisms linking pain severity to depression symptoms in women cancer survivors at a cancer center with a rural catchment area.

PURPOSE: Women cancer survivors, especially those in rural areas, with high levels of depression may be acutely susceptible to pain due to the ways they think, feel, and behave. The current study seeks to elucidate the relationship between symptoms of depression and pain severity in women cancer survivors, by examining the putative mediators involved in this relationship, specifically their self-efficacy for managing their health, how overwhelmed they were from life's responsibilities, and relational burden. METHODS: Self-report data were collected from 183 cancer survivors of breast, cervical, ovarian, or endometrial/uterine cancer, who were between 6 months and 3 years post-active therapy. RESULTS: Women cancer survivors with higher (vs. lower) symptoms of depression had more severe pain. Individual mediation analyses revealed that survivors with higher levels of depression felt more overwhelmed by life's responsibilities and had lower self-efficacy about managing their health, which was associated with greater pain severity. When all mediators were simultaneously entered into the same model, feeling overwhelmed by life's responsibilities significantly mediated the link between survivors' symptoms of depression and their pain severity. CONCLUSIONS: The relationship between symptoms of depression and pain severity in women cancer survivors may be attributed in part to their self-efficacy and feeling overwhelmed by life's responsibilities. Early and frequent assessment of psychosocial factors involved in pain severity for women cancer survivors may be important for managing their pain throughout the phases of cancer survivorship.

Elevated pain sensitivity is associated with reduced rapid eye movement (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 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 = .009), General Pain Sensitivity Indices (B = -3.069, P = .007), and Masseter Pain Pressure Threshold (B = 0.030, P = .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.

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.

Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3-5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.

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.

Sleep, Positive Affect, and Circulating Interleukin-6 in Women With Temporomandibular Joint Disorder.

OBJECTIVE: Systemic inflammation is commonly observed in idiopathic chronic pain conditions, including temporomandibular joint disorder (TMD). Trait positive affect (PA) is associated with lower inflammation in healthy controls, but those effects may be threatened by poor sleep. The associations between PA with proinflammatory cytokine activity and potential moderation by sleep in chronic pain are not known. We thus investigated the association between PA and circulating interleukin-6 (IL-6) and moderation of that association by sleep in a sample of women with TMD and sleep difficulties. METHODS: Participants (n = 110) completed the insomnia severity index and provided blood samples at five intervals throughout an evoked pain testing session. They then completed a 14-day diary assessing sleep and affect, along with wrist actigraphy. RESULTS: There was not a significant main effect of PA on resting or pain-evoked IL-6 (b = 0.04, p = .33). Diary total sleep time (b = -0.002, p = .008), sleep efficiency (b = -0.01, p = .005), sleep onset latency (b = 0.006, p = .010), and wake after sleep onset (b = 0.003, p = .033) interacted with PA to predict IL-6, such that PA inversely predicted IL-6 at higher levels of total sleep time and sleep efficiency and at lower levels of sleep onset latency and wake after sleep onset. Surprisingly, when sleep was poor, PA predicted greater IL-6. CONCLUSIONS: The potential salutary effects of PA on resting IL-6 erode when sleep is poor, underscoring the importance of considering sleep in conceptual and intervention models of TMD.

Clinical correlates of drug-related dreams in opioid use disorder.

BACKGROUND AND OBJECTIVES: Drug-related dreams are commonly reported by individuals in treatment for substance use disorders, which may be distressing. Existing evidence suggests that dream recollection may be influenced by clinically relevant phenomena, such as opioid use and withdrawal, general sleep disturbance, affective symptoms, and chronic pain. However, very few studies have explored drug-related dreams among individuals who screened positive for opioid use disorder (OUD). METHODS: Adults recruited from Amazon Mechanical Turk (MTurk) who screened positive for OUD (N = 154) completed a questionnaire about drug-related dreams, as well as measures assessing sleep, opioid use history, stress, anxiety, and chronic pain. χ2 analyses, one-way analysis of variance, and bivariate correlations, correcting for the false discovery rate, were used as appropriate to explore correlates of (1) recollecting a drug-related dream, and (2) experiencing post-dream craving and distress. RESULTS: Individuals who recollected a past-week drug-related dream were more likely to report other recent sleep disturbances, including poorer sleep quality, greater insomnia symptoms, and a higher risk for sleep apnea. Post-dream craving and distress were both associated with greater insomnia symptoms, poor sleep hygiene behaviors, and greater anxiety symptoms. Individuals who had ever experienced a drug-related dream (recently, or in their lifetime) were more likely to report a history of severe withdrawal, overdose, and intravenous opioid use. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Drug-related dreams were common among individuals in the present sample and were related to other clinically relevant phenomena. Interventions that treat co-occurring OUD, pain, sleep symptoms, and affective symptoms may improve overall well-being in this population.

A Preliminary Investigation of the Underlying Mechanism Associating Daily Sleep Continuity Disturbance and Prescription Opioid Use Among Individuals With Sickle Cell Disease.

BACKGROUND: There are emerging data indicating that sleep disturbance may be linked with an increase in opioid use. The majority of sickle cell disease (SCD) patients experience sleep disturbances, which can elevate pain severity and pain catastrophizing, both of which are important predictors of opioid consumption. PURPOSE: We conducted a preliminary investigation on the association between previous night sleep disturbance and short-acting opioid use, as well as the potential mediating roles of pain severity and pain catastrophizing. Because sex is associated with sleep disturbance, pain-related experiences, and opioid use, we also explored the potential moderating role of sex. METHODS: Participants were 45 SCD patients who were prescribed opioids. For 3 months, sleep diaries were collected immediately upon participants' awakening. Daily pain severity, pain catastrophizing, and prescription opioid use measures were collected before bedtime. RESULTS: Multilevel structural equation modeling revealed that wake time after sleep onset (WASO) during the previous night (Time 1) predicted greater short-acting opioid use during the next day (Time 2). Pain severity and pain catastrophizing measured during the next day (Time 2) also mediated the association between the two. Sex moderation analysis showed that the positive association between WASO and pain severity was largely driven by women. CONCLUSION: These findings provide some preliminary evidence as to the mechanism linking sleep continuity disturbance and opioid requirement in SCD patients. Future studies should replicate and extend these findings with clearer temporal information and employing more refined measures of sleep continuity and prescription opioid use in a larger sample.

Reward Responsiveness in Patients with Opioid Use Disorder on Opioid Agonist Treatment: Role of Comorbid Chronic Pain.

OBJECTIVE: Evidence suggests that blunted reward responsiveness may account for poor clinical outcomes in both opioid use disorder (OUD) and chronic pain. Understanding how individuals with OUD and comorbid chronic pain (OUD+CP) respond to rewards is, therefore, of clinical interest because it may reveal a potential point of behavioral intervention. METHODS: Patients with OUD (n = 28) and OUD+CP (n = 19) on opioid agonist treatment were compared on: 1) the Probabilistic Reward Task (an objective behavioral measure of reward response bias) and 2) ecological momentary assessment of affective responses to pleasurable events. RESULTS: Both the OUD and the OUD+CP groups evidenced an increase in reward response bias in the Probabilistic Reward Task. The rate of change in response bias across blocks was statistically significant in the OUD group (B = 0.06, standard error [SE] = 0.02, t = 3.92, P < 0.001, 95% confidence interval [CI]: 0.03 to 0.09) but not in the OUD+CP group (B = 0.03, SE = 0.02, t = 1.90, P = 0.07, 95% CI: -0.002 to 0.07). However, groups did not significantly differ in the rate of change in response bias across blocks (B = 0.03, SE = 0.02, t = 1.21, P = 0.23, 95% CI: -0.02 to 0.07). Groups did not significantly differ on state measures of reward responsiveness (P's ≥0.50). CONCLUSIONS: Overall, findings across objective and subjective measures were mixed, necessitating follow-up with a larger sample. The results suggest that although there is a reward response bias in patients with OUD+CP treated with opioid agonist treatment relative to patients with OUD without CP, it is modest and does not appear to translate into patients' responses to rewarding events as they unfold in daily life.

Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.

Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F(4,14) = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR > 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad.

The Role of Resilience in the Clinical Management of Chronic Pain.

Chronic pain affects more individuals than does cancer, heart disease, and diabetes combined. Yet, our treatment options remain remarkably limited. Often, highly effective psychotherapeutic approaches are limited by many barriers such as access, reimbursement, and acceptability; however, resilience-based positive activity interventions could offer a promising alternative. These interventions are engaging, non-stigmatizing, and do not require a mental health professional for their provision. This article reviews the new, but limited, research exploring the use of positive activity interventions for the treatment of patients with chronic pain. The related psychological and biological mechanisms are addressed, as are suggestions for more systematically evaluating the potential for positive activity interventions to become an adjunct to or stand-alone intervention strategy for patients with chronic pain.

Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis.

BACKGROUND: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. METHOD: Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. RESULTS: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). CONCLUSIONS: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT01383954 . Registered June 22, 2011.

Effects of insomnia disorder and knee osteoarthritis on resting and pain-evoked inflammatory markers.

Osteoarthritis is the most prevalent arthritic condition. Systemic inflammatory cytokines appear to have an important role in the onset and maintenance of the disease. Sleep disturbances are prevalent in osteoarthritis and associated with alterations in systemic inflammatory cytokines, suggesting a common pathophysiology across these conditions. A comparative investigation of the effects of insomnia disorder and osteoarthritis on pain-evoked cytokine responses has yet to be undertaken. We examined the influence of symptomatic knee osteoarthritis and insomnia disorder on resting C-reactive protein (CRP), interleukin (IL)-6, and IL-10 levels, and pain-evoked IL-6 and IL-10 responses. Participants were N=117 older adults (mean age=59.7years; 61.8% women) rigorously evaluated for knee osteoarthritis and insomnia disorder using established diagnostic guidelines. Results revealed no association of osteoarthritis or insomnia disorder with CRP. Resting IL-6 was greater in osteoarthritis participants versus those without osteoarthritis, although this association was largely attributable to BMI. IL-10 was highest among participants with osteoarthritis or insomnia disorder. Growth curve modeling revealed that participants with insomnia disorder had greater pain-evoked IL-6 responses than participants without insomnia disorder or osteoarthritis. These findings highlight the utility of laboratory pain testing methods for understanding individual differences in inflammatory cytokines. Moreover, our findings provide evidence for amplified pain-evoked pro-inflammatory cytokine reactivity among older adults with clinically diagnosed insomnia disorder, even after controlling for individual differences in BMI and age. Additional research will be required determine whether an amplified pain-related cytokine response contributes to OA, and possibly other age-related disease, associated with insomnia disorder.

Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization.

OBJECTIVE: Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures. METHODS: A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure-pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1-2 versus 3-4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30). RESULTS: Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain-sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race. CONCLUSION: The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate-to-severe radiographic evidence of pathologic changes of knee OA.

Preliminary Validation of the Pain Relief Motivation Scales.

OBJECTIVES: Pain typically prompts individuals to seek relief. This study aimed to develop and psychometrically validate the Pain Relief Motivation Scales, applying revised "reinforcement sensitivity theory" to measure the neuropsychological systems underlying motivation for pain relief. We hypothesized a 6-factor structure based on previous work, including one Behavioral Inhibition System (BIS) factor, one Fight-Flight-Freeze System factor, and 4 Behavioral Activation System (BAS) factors. METHODS: Items were generated by adapting the reinforcement sensitivity theory of personality questionnaire for relevance to pain relief. Adults with chronic pain were recruited internationally to participate in online survey batteries at baseline and 1 week later in 2021. We randomly split the sample to conduct exploratory factor analysis (n = 253) and confirmatory factor analysis (n = 253). Psychometric properties were estimated using the full sample (N = 506). RESULTS: Parallel analysis revealed that a 5-factor structure best fits the data (21 items): (1) hopelessness about pain relief (BIS), (2) hesitancy for engaging in pain treatments (BIS), (3) persistence in engaging in pain treatments (BAS), (4) relief reactivity (BAS), and (5) risky relief seeking (BAS). Acceptable internal consistency (Cronbach alpha = 0.68 to 0.80) and test-retest reliability (Intraclass correlation coefficients = 0.71 to 0.88) were observed. Construct validity varied from weak to moderate ( r = 0.02 to 0.45). CONCLUSION: As the first attempt to create an instrument measuring neuropsychological systems underlying motivation for pain relief, the findings show that additional work is needed to refine theory and psychometric rigor in this area. Cautiously, the results suggest that a BIS-BAS model, with minimal Fight-Flight-Freeze System contributions, might be useful for understanding the motivation for relief.

The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder.

BACKGROUND: The Divided or Single Exposure (DOSE) trial is a double-blind, placebo-controlled examination of once versus split dosing of methadone for comorbid pain and opioid use disorder (OUD) among persons receiving methadone for OUD treatment. METHODS: This multisite trial consists of a 12-week active intervention phase and 6-month follow-up period. Persons receiving methadone who endorse clinically-significant chronic pain are randomized into once-daily dosing or split dosing that is managed remotely via an electronic pillbox. Clinical pain is assessed weekly and using ecological momentary assessments. Experimentally-evoked pain is assessed using a quantitative sensory testing battery. Additional outcomes related to OUD, including withdrawal and craving, are also collected. RESULTS: The study hypothesizes that persons assigned to the split dosing condition will report lower pain and opioid withdrawal relative to persons assigned to the traditional once-daily dosing strategy. CONCLUSIONS: Split dosing is a relatively common technique in OUD treatments; therefore, if data support this hypothesis, there is high potential for implementation.

Sleep Disruption Moderates the Daily Dynamics of Affect and Pain in Sickle Cell Disease.

Persons with sickle cell disease (SCD) often experience pain that can interfere with quality of life and daily activities. Pain can modulated by affect and sleep continuity; however, few studies have explored how these factors complementarily influence pain in adults with SCD. The study aims were to investigate 1) whether pain levels were heightened on days characterized by low positive affect and high negative affect, and 2) whether the relationship between affect and pain was intensified following nights of disrupted sleep. Adults with SCD (N = 25) completed ecological momentary assessments and daily sleep diaries. Mixed models were used to analyze the main and interactive effects of daily affect (positive affect and negative affect) and sleep disruption (wake after sleep onset and frequency of awakenings) on both daily average pain and daily maximum pain. Results suggested that daily average pain and maximum pain tended to be higher on days of low positive affect and high negative affect. Furthermore, the frequency of nocturnal awakenings moderated the relationship between positive affect and pain. On days where there were higher frequencies of nocturnal awakenings, low positive affect was associated with both average and maximum pain; however, this association was not observed with lower frequencies of nocturnal awakenings. The association between negative affect and maximum pain was also stronger at higher levels of awakenings. Results highlight the relevance of adjunctive interventions that target affect among populations with SCD and further suggest that sleep continuity may further facilitate these interventions, highlighting the importance of multimodal treatments. PERSPECTIVE: This study examined the effects of affect and sleep on pain among adults with sickle cell disease (SCD). Higher pain occurred on days of low positive affect and high negative affect, particularly following nights of more frequent awakenings. These findings emphasize the importance of addressing affect and sleep in SCD treatment.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis.

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current pilot mechanistic randomized controlled trial was to test the effects of a positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis. Participants included 44 patients with a physician-confirmed diagnosis of rheumatoid arthritis (n = 29 included in functional magnetic resonance imaging (fMRI) analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre-and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Savoring significantly reduced experimental pain intensity ratings relative to rest (P < .001). Savoring also increased cerebral blood flow in the ventromedial prefrontal cortex and increased connectivity between the ventromedial prefrontal cortex and caudate during noxious thermal stimulation relative to Slow Breathing (z = 2.3 voxelwise, false discovery rate cluster corrected P = .05). Participants in the Savoring condition also reported significantly increased positive emotions (ps < .05) and reduced anhedonic symptoms (P < .01) from pre- to post-intervention. These findings suggest that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations. PERSPECTIVE: Savoring Meditation is a novel positive emotion-enhancing intervention designed for patients with chronic pain. The present findings provide preliminary evidence that Savoring Meditation is acutely analgesic, and engages neural and subjective emotional targets that are relevant to pain self-management. Future work should evaluate the clinical translation of these findings.

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.