Opioid-treated Chronic Pain Patients Research Articles

Zoom-Based Mindfulness-Oriented Recovery Enhancement Plus Just-in-Time Mindfulness Practice Triggered by Wearable Sensors for Opioid Craving and Chronic Pain.

The opioid crisis in the USA remains severe during the COVID-19 pandemic, which has reduced access to evidence-based interventions. This Stage 1 randomized controlled trial (RCT) assessed the preliminary efficacy of Zoom-based Mindfulness-Oriented Recovery Enhancement (MORE) plus Just-in-Time Adaptive Intervention (JITAI) prompts to practice mindfulness triggered by wearable sensors (MORE + JITAI). Opioid-treated chronic pain patients (n = 63) were randomized to MORE + JITAI or a Zoom-based supportive group (SG) psychotherapy control. Participants completed ecological momentary assessments (EMA) of craving and pain (co-primary outcomes), as well as positive affect, and stress at one random probe per day for 90days. EMA probes were also triggered when a wearable sensor detected the presence of physiological stress, as indicated by changes in heart rate variability (HRV), at which time participants in MORE + JITAI were prompted by an app to engage in audio-guided mindfulness practice. EMA showed significantly greater reductions in craving, pain, and stress, and increased positive affect over time for participants in MORE + JITAI than for participants in SG. JITAI-initiated mindfulness practice was associated with significant improvements in these variables, as well as increases in HRV. Machine learning predicted JITAI-initiated mindfulness practice effectiveness with reasonable sensitivity and specificity. In this pilot trial, MORE + JITAI demonstrated preliminary efficacy for reducing opioid craving and pain, two factors implicated in opioid misuse. MORE + JITAI is a promising intervention that warrants investigation in a fully powered RCT. This study is registered on ClinicalTrials.gov (NCT04567043).

The Mindful Reappraisal of Pain Scale (MRPS): Validation of a New Measure of Psychological Mechanisms of Mindfulness-Based Analgesia.

Mindfulness is theorized to decrease the affective amplification of chronic pain by facilitating a shift from emotionally-laden, catastrophic pain appraisals of nociceptive input to reappraising chronic pain as an innocuous sensory signal that does not signify harm. Understanding of these hypothetical psychological mechanisms of mindfulness-based analgesia has been limited by a lack of direct measures. We conducted a series of psychometric and experimental studies to develop and validate the Mindful Reappraisal of Pain Sensations Scale (MPRS). After item generation, we conducted exploratory and confirmatory factor analyses of the MRPS in samples of opioid-treated chronic pain patients both before (n=450; n=90) and after (n=222) participating in Mindfulness-Oriented Recovery Enhancement (MORE). We then examined the convergent and divergent validity of the MRPS. Finally, in data from a randomized clinical trial (n=250), the MRPS was tested as a mediator of the effects of MORE on reducing chronic pain severity. Exploratory and confirmatory factor analyses demonstrated the single-factor structure of the MRPS. The MRPS also evidenced convergent and divergent validity. Mindfulness training through MORE significantly increased MRPS scores relative to supportive psychotherapy (F4,425.03 = 16.15, p < .001). Changes in MRPS scores statistically mediated the effect of MORE on reducing chronic pain severity through 9-month follow-up. Taken together, these studies demonstrate that the MRPS is a psychometrically sound and valid measure of novel analgesic mechanisms of mindfulness including attentional disengagement from affective pain appraisals and interoceptive exposure to pain sensations.

Association between opioid use disorder and blunted heart rate variability among opioid-treated chronic pain patients.

Given the severity of the ongoing opioid epidemic, it is essential to understand the mechanisms of risk for development and maintenance of opioid use disorder (OUD). The aim of the current large-scale psychophysiological investigation was to test whether patients with OUD had lower resting-state high-frequency heart rate variability (HF-HRV) than those without OUD, controlling for sociodemographic and clinical confounds. Additionally, we tested whether HF-HRV was associated with opioid craving in this population. Participants in this cross-sectional study were 490 chronic pain patients (50.4% female) treated with long-term opioid therapy. OUD diagnosis was determined by psychiatric interview. HF-HRV was measured at resting baseline. We computed the association between OUD and resting-state HF-HRV, controlling for age, gender, race, pain severity, emotional distress and opioid dose. Opioid craving was measured with visual analogue scales to assess whether HF-HRV was associated with craving. Results showed that resting HF-HRV was significantly lower for patients with OUD than for those without OUD (p < 0.001, d = 0.36), indicating deficits in autonomic flexibility. OUD diagnosis (p = 0.002) and OUD severity (p = 0.03) were associated with lower HF-HRV in regression models accounting for a range of confounders. Additionally, lower HF-HRV was significantly (but weakly) correlated with heightened opioid craving (r = -0.166, p < 0.001). Overall, findings suggest that resting-state HF-HRV may serve as a valid biomarker of addiction among people on long-term opioid therapy.

Understanding and restoring dopaminergic function in fibromyalgia patients using a mindfulness-based psychological intervention: a [18F]-DOPA PET study. Study protocol for the FIBRODOPA study\u2014a randomized controlled trial

BackgroundFibromyalgia (FM) is a very prevalent and debilitating chronic pain disorder that is difficult to treat. Mindfulness-based techniques are regarded as a very promising approach for the treatment of chronic pain and in particular FM. The Mindfulness-Oriented Recovery Enhancement (MORE) intervention, a mindfulness-based group intervention, has shown beneficial effects in opioid-treated chronic pain patients, including reduced pain severity, functional interference, and opioid dosing, by restoring neurophysiological and behavioral responses to reward. The first evidence for a hypodopaminergic state and impaired reward processing in FM has been reported. However, little is known about its impact on dopamine (DA) function and in particular with regard to DA responses to monetary reward in FM. The aim of the present study protocol is to evaluate if MORE is able to restore the DA function in FM patients, in particular with regard to the DA responses to reward, and to reduce pain and mood complaints in FM.MethodsThe present study is a multi-center interventional RCT with 3 time points: before the intervention, after completion of the intervention, and 3 months after completion of the intervention. Sixty-four FM patients will be randomly assigned to either the MORE intervention (N = 32) or a non-intervention control group (N = 32). Additionally, a comparison group of healthy women (N = 20) for PET measures will be enrolled and another group of healthy women (N = 15) will do the ambulatory assessments only. The MORE intervention consists of eight 2-h-long group sessions administered weekly over a period of 8 weeks. Before and after the intervention, FM participants will undergo [18F] DOPA positron emission tomography (PET) and functional MR imaging while performing a reward task. The primary outcome will be endogeneous DA changes measured with [18F] DOPA PET at baseline, after the intervention (after 8 weeks for the non-intervention control group), and at 3 months’ follow-up. Secondary outcomes will be (1) clinical pain measures and FM symptoms using standardized clinical scales; (2) functional brain changes; (3) measures of negative and positive affect, stress, and reward experience in daily life using the ambulatory assessment method (AA); and (4) biological measures of stress including cortisol and alpha-amylase.DiscussionIf the findings of this study confirm the effectiveness of MORE in restoring DA function, reducing pain, and improving mood symptoms, MORE can be judged to be a promising means to improve the quality of life in FM patients. The findings of this trial may inform health care providers about the potential use of the MORE intervention as a possible non-pharmacological intervention for FM.Trial registrationClinicalTrials.govNCT 04451564. Registered on 3 July 2020. The trial was prospectively registered.

Mindfulness-oriented recovery enhancement improves negative emotion regulation among opioid-treated chronic pain patients by increasing interoceptive awareness

ObjectiveLong-term opioid therapy presents health risks for people with chronic pain. Some chronic pain patients escalate their opioid dose to regulate negative emotions. Therefore, emotion regulatory strategies like reappraisal are key treatment targets for this population. Mindfulness has been shown to enhance reappraisal, but the mechanisms of action are unknown. This study was a secondary analysis of data from a randomized, controlled trial of Mindfulness-Oriented Recovery Enhancement (MORE) to test a specific postulate of the Mindfulness-to-Meaning Theory: that mindfulness-based interventions promote reappraisal, via interoceptive self-regulation, as a means of decreasing emotional distress. MethodsNinety-five patients with opioid-treated chronic pain (age = 56.8 ± 11.7, 66% female) were randomized to 8 weeks of MORE or Support Group (SG) psychotherapy. An interoceptive awareness latent variable was constructed from the Multidimensional Assessment of Interoceptive Awareness (MAIA). Next, interoceptive self-regulation was assessed as a mediator of the effect of MORE on post-treatment reappraisal, and then reappraisal was examined as a mediator of change in distress through 3-month follow-up. ResultsMORE participants had greater improvements in interoceptive awareness than the SG as measured by the interoceptive awareness latent variable (β = 0.310, p = 0.008) and by the self-regulation MAIA subscale (β = 0.335, p = 0.001). The effect of MORE on treatment-induced increases in reappraisal was mediated by increased interoceptive self-regulation (indirect effect: β = 0.110, p = 0.030). In turn, decreases in distress through 3-month follow-up were mediated by increases in reappraisal (indirect: β = −0.136, p = 0.031). ConclusionMORE facilitated reappraisal of distress by enhancing interoceptive self-regulation, supporting a central mechanistic causal pathway specified by the Mindfulness-to-Meaning Theory.

Toward safer opioid prescribing: effects of the TOWER intervention on HIV care providers

ABSTRACT Rates of opioid use disorder and associated deaths remain alarmingly high. Measures to address the epidemic have included reductions in opioid prescribing, in part guided by the Centers for Disease Control Opioid Prescribing Guideline (CDCG). While reductions in over-prescribing have occurred, these measures have also resulted in decreased access and adverse outcomes for some stable opioid-treated chronic pain patients. The TOWard SafER Opioid Prescribing (TOWER) intervention was designed to support HIV primary care providers in use of the CDCG and in decision-making and patient–provider communication regarding safe opioid prescribing. Eleven HIV primary care providers and 40 of their patients were randomized into intervention and control groups. Transcripts from 21 patient visits were analyzed, focusing on opioid and pain-related communications. Findings from this research indicate greater alignment with the CDCG among visits carried out with providers in the TOWER intervention group. However, control group visits were notably consistent with guideline recommendations in several key areas. Differences observed between the intervention and control group visits demonstrate intervention strengths, as well as areas where additional work needs to be done to ensure prescribing and communication consistent with the CDCG.

Prescription opioid misusers exhibit blunted parasympathetic regulation during inhibitory control challenge.

Among opioid-treated chronic pain patients, response inhibition deficits in emotional contexts may contribute to opioid misuse. Using high-frequency heart rate variability (HF-HRV) to index-impaired response inhibition, we examined associations between opioid misuse and response inhibition in emotional and neutral contexts in a sample of opioid-treated chronic pain patients. Chronic pain patients taking opioid analgesics (N = 97) for ≥ 90days completed an Emotional Go/NoGo task that presented an inhibitory control challenge in the context of neutral, opioid, negative affective, and positive affective background images while HF-HRV was computed. Opioid misuse and craving were assessed. Using a validated cut-point on the Current Opioid Misuse Measure, participants were classified as opioid misusers or non-misusers. Opioid misuse was examined as a predictor of behavioral and HF-HRV metrics of response inhibition. Negative affective and opioid images elicited more errors of commission (p = .002, η2partial = .16) and slowed reaction times (p = .045, η2partial = .09) compared to neutral and positive affective images, respectively. Though no between-group behavioral differences were observed on the task, opioid misusers exhibited significantly blunted phasic HF-HRV during the task relative to non-misusers (p = .027, η2partial = .11). HF-HRV during the task was significantly inversely associated with opioid craving. It was not clear whether these autonomic findings reflected a durable phenotypic difference between groups or between-group differences in opioid dosing and withdrawal. Reduced parasympathetic regulation during inhibitory control challenge may indicate heightened opioid misuse risk among opioid-treated chronic pain patients.

Adverse childhood experiences predict autonomic indices of emotion dysregulation and negative emotional cue-elicited craving among female opioid-treated chronic pain patients.

Through autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N = 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.

Behavioral preference for viewing drug v. pleasant images predicts current and future opioid misuse among chronic pain patients.

The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal. The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often. At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up. These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.

Autonomic and affective mediators of the relationship between mindfulness and opioid craving among chronic pain patients.

Prescription opioid misuse among chronic pain patients is undergirded by self-regulatory deficits, affective distress, and opioid-cue reactivity. Dispositional mindfulness has been associated with enhanced self-regulation, lower distress, and adaptive autonomic responses following drug-cue exposure. We hypothesized that dispositional mindfulness might serve as a protective factor among opioid-treated chronic pain patients. We examined heart-rate variability (HRV) during exposure to opioid cues and depressed mood as mediators of the association between dispositional mindfulness and opioid craving. Data were obtained from a sample of chronic pain patients (N = 115) receiving long-term opioid pharmacotherapy. Participants self-reported opioid craving and depression, and HRV was measured during an opioid-cue dot-probe task. Dispositional mindfulness was significantly positively correlated with HRV, and HRV was significantly inversely associated with opioid craving. Dispositional mindfulness was significantly negatively correlated with depression, and depression was significantly positively correlated with opioid craving. Path analysis revealed significant indirect effects of dispositional mindfulness on craving through both HRV and depression. Dispositional mindfulness may buffer against opioid craving among chronic pain patients prescribed opioids; this buffering effect may be a function of improved autonomic and affective responses. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Effects of Mindfulness-Oriented Recovery Enhancement Versus Social Support on Negative Affective Interference During Inhibitory Control Among Opioid-Treated Chronic Pain Patients: A Pilot Mechanistic Study.

Among opioid-treated chronic pain patients, deficient response inhibition in the context of emotional distress may contribute to maladaptive pain coping and prescription opioid misuse. Interventions that aim to bolster cognitive control and reduce emotional reactivity (e.g., mindfulness) may remediate response inhibition deficits, with consequent clinical benefits. To test the hypothesis that a mindfulness-based intervention, Mindfulness-Oriented Recovery Enhancement (MORE), can reduce the impact of clinically relevant, negative affective interference on response inhibition function in an opioid-treated chronic pain sample. We examined data from a controlled trial comparing adults with chronic pain and long-term prescription opioid use randomized to either MORE (n = 27) treatment or to an active support group comparison condition (n = 30). Participants completed an Emotional Go/NoGo Task at pre- and post-treatment, which measured response inhibition in neutral and clinically relevant, negative affective contexts (i.e., exposure to pain-related visual stimuli). Repeated-measures analysis of variance indicated that compared with the support group, participants in MORE evidenced significantly greater reductions from pre- to post-treatment in errors of commission on trials with pain-related distractors relative to trials with neutral distractors, group × time × condition F(1,55) = 4.14, p = .047, η2partial = .07. Mindfulness practice minutes and increased nonreactivity significantly predicted greater emotional response inhibition. A significant inverse association was observed between improvements in emotional response inhibition and treatment-related reductions in pain severity by 3-month follow-up. Study results provide preliminary evidence that MORE enhances inhibitory control function in the context of negative emotional interference.

Dispositional mindfulness and prescription opioid misuse among chronic pain patients: Craving and attention to positive information as mediating mechanisms

ObjectivesOpioid-treated chronic pain patients may be at risk for prescription opioid misuse due to heightened opioid craving coupled with deficits in attention to naturally rewarding, positive stimuli. Conversely, dispositional mindfulness, which is associated with reduced craving and increased responsiveness to natural rewards, may serve as a protective factor and buffer opioid misuse risk. The current investigation aimed to examine the association between mindfulness and opioid misuse, and to test opioid craving and attention to positive information as mediators of this relationship. MethodsThis cross-sectional analysis examined data obtained from a sample of civilian opioid-treated chronic pain patients in the Southeastern U.S. (Sample 1: N = 115), as well as civilian (Sample 2: N = 141) and military samples in the Intermountain West (Sample 3: N = 44). Pearson correlations and path analyses were employed to test relations among participant self-reports on the Current Opioid Misuse Measure (COMM), the Five Facet Mindfulness Questionnaire (FFMQ), two measures of opioid craving, and the Attention to Positive and Negative Information Scale (APNIS). ResultsAcross all three samples, dispositional mindfulness was significantly inversely associated with opioid misuse (N = 300, r = −0.36, p < .001). Reduced opioid craving and increased attention to positive information mediated the association between dispositional mindfulness and opioid misuse. DiscussionDispositional mindfulness may buffer opioid misuse risk by attenuating opioid craving and enhancing attention to naturally rewarding stimuli.

Enhancing Natural Reward Responsiveness Among Opioid Users Predicts Chronic Pain Relief: EEG Analyses From a Trial of Mindfulness-Oriented Recovery Enhancement.

Although opioid-treated chronic pain patients evidence blunted responsiveness to natural rewards, focusing on naturally rewarding stimuli can produce analgesia in these patients. A prior randomized controlled trial (RCT) demonstrated that a social work intervention-Mindfulness-Oriented Recovery Enhancement (MORE)-enhanced natural reward processing as indicated by event-related brain potentials (ERPs). The aim of the present study was to perform a secondary data analysis on ERPs collected in this RCT to explore whether improvements in electrocortical response to natural reward predicted pain relief. The sample for this secondary analysis included opioid-treated chronic pain patients with complete ERP data (N = 29). Participants were randomized to 8 weeks of MORE or a support group control condition, and ERPs to images representing naturally rewarding stimuli were measured before and after 8 weeks of treatment. We explored associations between changes in brain reward response, chronic pain symptoms, and pain coping. Increases in ERP reward response were significantly associated with decreased pain severity from pretreatment to posttreatment (β = -.48, p = .007) and improvements in pain catastrophizing (β = -.36, p = .05) and diverting attention as a means of pain coping (β = .38, p = .043). Increased ERP reward response predicted decreased pain interference by 3-month follow-up (β = -.37, p = .048). Chronic pain may be alleviated by enhancing brain response to natural rewards.

Prescription opioid misusing chronic pain patients exhibit dysregulated context-dependent associations: Investigating associative learning in addiction with the cue-primed reactivity task

BackgroundAssociative learning undergirds the development of addiction, such that drug-related cues serve as conditioned stimuli to elicit drug-seeking responses. Plausibly, among opioid misusing chronic pain patients, pain-related information may serve as a conditioned stimulus to magnify opioid cue-elicited autonomic and craving responses through a process of second-order conditioning. MethodsWe utilized a novel psychophysiological probe of pain-opioid conditioned associations, the Cue-Primed Reactivity (CPR) task. In this task, participants were presented with images as primes (200 ms) and cues (6000 ms) in pairs organized in four task blocks: “control-opioid,” “pain-opioid,” “control-pain,” and “opioid-pain.” Opioid-treated chronic pain patients (N = 30) recruited from an Army base in the Western United States were classified as opioid misusers (n = 17) or non-misusers (n = 13) via a validated cutpoint on the Prescription Drug Use Questionnaire (PDUQ; Compton et al., 2008). Opioid misuse status was examined as a predictor of HRV, craving, and mood responses on the CPR task. ResultsHRV increased to a greater extent during the pain-opioid block compared to the control-opioid block for non-misusers compared to misusers (p = .003, η2partial = 0.27). In contrast, craving increased to a greater extent from baseline to the pain-opioid block for misusers than for non-misusers (p = .03, η2partial = .16). ConclusionsFindings suggest that opioid-treated chronic pain patients exhibit Pavlovian conditioned responses to opioid cues strengthened by an associative learning process of second-order conditioning when primed by pain-related images. This pain-opioid contingency appears to become disrupted among individuals who engage in opioid misuse, such that opioid-related stimuli elicit motivational responses irrespective of pain-related contextual stimuli.

Mindfulness-Oriented Recovery Enhancement Reduces Opioid Attentional Bias Among Prescription Opioid-Treated Chronic Pain Patients

Objective: Opioid-misusing chronic pain patients who are treated with opioid analgesics selectively attend to opioid-related cues. This opioid attentional bias (AB) is a maladaptive cognitive process that can lead to automatic, habitual misuse of opioids. The aim of this secondary data analysis was to explore the effects of a novel social work intervention, Mindfulness-Oriented Recovery Enhancement (MORE), on posttreatment opioid AB among a subgroup of chronic pain patients who exhibit attentional reactivity to opioid cues prior to treatment. MORE is a group-therapy program that integrates training in mindfulness, reappraisal, and savoring techniques. Method: Data were obtained from a sample of chronic pain patients (N = 115) who participated in a randomized controlled trial and were randomized to an 8-week MORE intervention or an 8-week support group. A dot-probe task assessed opioid AB for opioid-related cues, and the Current Opioid Misuse Measure assessed changes in opioid-misusing behaviors from pretreatment to 3-month follow-up. Results: Pretreatment opioid AB moderated the effect of treatment on changes in opioid AB. Among participants with a positive 200 millisecond (ms) opioid AB at pretreatment (n = 71), MORE was associated with significantly greater reductions in 200 ms opioid AB than the support group from pretreatment to posttreatment, but no changes in 2,000 ms opioid AB were observed. Decreases in 200 ms opioid AB over the course of treatment predicted reduced opioid misuse by 3-month follow-up. Conclusions: This exploratory study provides preliminary evidence that a mindfulness-oriented intervention may significantly reduce opioid AB.

Pain, hedonic regulation, and opioid misuse: Modulation of momentary experience by Mindfulness-Oriented Recovery Enhancement in opioid-treated chronic pain patients

BackgroundGiven the risk of opioid misuse among chronic pain patients being treated with long-term opioid pharmacotherapy, non-pharmacological treatments are needed. Further, in light of hedonic deficits in this population, therapies that enhance positive affect may be useful. The purpose of this study was to examine effects of a Mindfulness-Oriented Recovery Enhancement (MORE) intervention on ecological momentary assessments (EMA) of pain and positive affective experience, and to determine if changes in pain, affect, and their interaction were associated with opioid misuse at post-treatment. MethodsThis study examined unpublished EMA data from a subset of participants (N=55) in a previously published RCT (NCT01505101) of MORE versus a support group (SG) control. Across 8 weeks of treatment, patients completed up to 224 EMA measures of pain and affect. Multilevel models and generalized estimating equations examined effects of treatment on momentary pain and positive affect, and generalized linear models examined associations between pain and affect and changes in opioid misuse by post-treatment. ResultsPatients in MORE reported significantly greater improvements in momentary pain (p=0.01) and positive affect (p=0.004) than patients in the SG. Further, over the entire course of treatment, patients in MORE were significantly more likely to exhibit positive affect regulation (OR=2.75) than patients in the SG. Finally, improvements in positive affect (but not pain) over the course of intervention were associated with reduced risk of misusing opioids by post-treatment (p=0.02). ConclusionMORE may be a useful non-pharmacological treatment for pain and hedonic deficits among chronic pain patients at risk for opioid misuse.

A KCNJ6 (Kir3.2, GIRK2) gene polymorphism modulates opioid effects on analgesia and addiction but not on pupil size

KCNJ6 coding for potassium inwardly rectifying channels (Kir3.2, GIRK2) is important for opioid receptor transmission. The KCNJ6 rs2070995 AA genotype has been associated with increased opioid analgesic requirements in Japanese. We analyzed its consequences for other opioid effects. Genotyping was done in 85 methadone-substituted former heroin addicts, 352 opioid-treated chronic pain patients, and in 51 healthy volunteers where miotic effects of levomethadone had been measured. Expression of Kir3.2 in the Edinger-Westphal nucleus of rat brains was analyzed by means of immunohistochemistry. Average daily methadone substitution doses during the first therapy year were larger in the AA genotype (n=4, 119.7+/-49.6 mg/day) than in other rs2070995 genotypes (77.5+/-26.2 mg/day, P=0.003) whereas AA carriers lacked opioid withdrawal symptoms. A similar tendency toward less opioid effectiveness was observed toward higher opioid dosing demands for analgesia in the AA genotype (n=17, opioid dose 2.03+/-0.45 log mg oral morphine equivalents per day, controls: 1.81+/-0.52 log mg oral morphine equivalents/day, P=0.093). In contrast, no pharmacogenetic effects were observed on miotic opioid effects. This could be traced back to the absence of Kir3.2 from the Edinger-Westphal nucleus in rat brains, a key cerebral structure governing pupil constriction. The association of the KCNJ6 rs2070995 AA genotype with increased opioid requirements extends from analgesia to opiate substitution therapy. Opioid induced miosis is exempted for molecular histological reasons.

Pain and Opioid Addiction: What is the Connection?

Addiction to opioid analgesics is an important and yet underinvestigated clinical issue, which has substantial implications in opioid therapy for chronic pain management. Problematic opioid use, including compulsive opioid seeking and addiction, arises in some fraction of opioid-treated chronic pain patients. The connection between chronic pain and opioid addiction is a complex interplay between psychological, epidemiological, and neurobiological factors. Herein, we explore this critical relationship.

An update on the role of opioids in the management of chronic pain of nonmalignant origin

To summarize and reflect over primarily recent epidemiological and randomized controlled trials in opioid-treated chronic nonmalignant pain patients, focusing on effects, side effects, risks and long-term consequences of the treatment. In the western world opioids are increasingly being used for long-term treatment of chronic nonmalignant pain. While the long-term benefits of opioids regarding pain relief, functional capacity and health-related quality of life still remain to be proven, studies are emerging that describe serious long-term consequences such as addiction, opioid-induced hyperalgesia, cognitive disorders, and suppression of the immune and reproductive systems. Much more research is needed concerning long-time effects and consequences of opioid therapy in chronic nonmalignant pain patients; however, some clear warning signals have been sent out within recent years.

(891): An observational US survey (GI BURDEN) to characterize the burden of illness associated with opioid-induced bowel dysfunction and laxative use

While the benefits of opioids for chronic pain management are widely acknowledged, the frequency, severity and impact of associated gastrointestinal (GI) side effects remain poorly characterized. In the US, no therapy is approved to directly inhibit these side effects. Laxatives are used, but their utility may be limited, particularly over an extended time period. GI BURDEN (GastroIntestinal BUrden in patients Receiving opioids: Descriptive Evidence of unmet Need), a prospective cross-sectional and longitudinal observational survey, is currently underway in North America to assess the burden of illness resulting from opioid-induced bowel dysfunction (OBD) and laxative use. Patients (n=522) prescribed opioids for ≥30 days for chronic pain, experiencing constipation related to opioid use, and using a laxative on ≥2 days/week in the last 4 weeks were recruited to the 8-week observational phase of the study. Those enrolled completed QoL questionnaires at clinic visits, and recorded GI symptoms daily using an interactive voice response system. Interim analysis of 350 patients who have completed at least 4 weeks of observation revealed that, in spite of laxative use, over one-half of patients reported constipation on at least 50% of days. Symptoms of straining, false alarm, incomplete evacuation and hard/dry stools were reported by >50% of patients every week of the observation period. Beyond constipation, the most common GI symptoms were lower abdominal pain, bloating, and abdominal fullness, with 35-40% of patients reporting them as moderate–severe. The majority of patients (85–90%) reported cramping, bloating, and excessive gas associated with laxative treatment, with over a third considering these side effects moderate or severe. These interim data suggest opioid-treated chronic pain patients commonly experience GI symptoms, particularly constipation, despite regular laxative use. Laxatives themselves were also shown to be associated with undesirable GI side effects thus adding to the burden of illness for many patients.