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Aims: Despite a strong theoretical link between opioid craving and pain, little is known about the temporal relationship between pain and craving and the acute experience of pain in the context of methadone treatment. Using a cross‐over design, the current study evaluated the time course of pain and craving and objective experience of pain as a function of the last methadone dose. Methods: Participants (n = 20) presented for the study in the morning and either received methadone dose as scheduled or delayed dose until the afternoon. During the 4‐h study visit, participants completed a series of tasks, including repeated assessment of pain and craving at 0, +40, +70, +130, +160 and +240 min and a cold pressor test (CPT) at +15 and +220 min. Results: Separate mixed model results demonstrated no effect of dosing condition on craving; however, there was a significant dosing condition by time interaction (F(5,209) = 3.38, P =.006) such that pain increased over time in the delayed methadone condition but decreased in time in the scheduled methadone condition. A mixed model predicting self‐reported pain revealed a three‐way interaction between dosing condition, craving and time (F(5,197) = 2.39, P =.039) explained by a positive association between craving and pain at each time point (except 240 min) in delayed condition (P‐range =.004–.0001). A separate mixed model on CPT data indicated a significant condition by time interaction such that pain threshold decreased in the delayed, but not scheduled, condition (F(1,57) = 4.01, P =.050). Conclusions: These preliminary findings highlight the potential for increased risks after even a short delay in receiving a methadone dose. [ABSTRACT FROM AUTHOR]

A re‐examination of clinical principles of long‐term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function and health) but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through antinociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward/antireward and nociceptive/antinociceptive systems. This opioid‐induced chronic pain syndrome (OICP) can persist/progress whether LTOT dose is maintained at the same level, increased, decreased or discontinued. Current conceptualization of LTOT as a straightforward long‐term analgesic therapy appears incongruous in view of the complex mechanisms of opioid action, LTOT dependence and OICP. LTOT can be more appropriately conceptualized as therapeutic induction and maintenance of an adaptive LTOT dependence for functional improvement irrespective of analgesic benefits. Adaptive LTOT dependence should be ideally used for a limited time to achieve maximum functional recovery and deprescribed while maintaining functional gains. Patients on LTOT should be regularly re‐evaluated to identify if maladaptive LTOT dependence with OICP has diminished any functional gains or leads to ineffectiveness. Ineffective LTOT (with maladaptive LTOT dependence) should be modified to make it safer and more effective. An adequately functional life without opioids is the ideal healthy long‐term goal for both LTOT initiation and LTOT modification. [ABSTRACT FROM AUTHOR]

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long‐term opioid therapy who develop marked tolerance to opioid‐induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain‐ and opioid‐induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid‐related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis. [ABSTRACT FROM AUTHOR]

The editorial in the British Journal of Clinical Pharmacology addresses the challenges of opioid use disorder (OUD) and chronic pain in the context of the opioid crisis. It highlights the strong association between chronic pain and OUD, the impact of pain on treatment outcomes, and the need for tailored pain assessment strategies for individuals with OUD. The special issue explores various interventions, including the use of clonidine for acute pain management, Mindfulness-Oriented Recovery Enhancement (MORE) for long-term therapy, and the potential of psychedelic medications and glial modulators in treating OUD and chronic pain. The authors emphasize the importance of further research to develop innovative approaches for effective pain management in individuals with OUD. [Extracted from the article]

Background Cognitive behavioral therapy for chronic pain (CBT-CP) has a strong evidence base, but little is known about when treatment benefits are achieved. The present study is a secondary analysis of individuals with chronic back pain recruited for a noninferiority trial comparing interactive voice response (IVR) CBT-CP with in-person CBT-CP. Methods On the basis of data from daily IVR surveys, a clinically meaningful change was defined as a 30% reduction in pain intensity (n = 108) or a 45% increase in daily steps (n = 104) compared with the baseline week. We identified individuals who achieved a meaningful change at any point during treatment, and then we compared those who maintained a meaningful change in their final treatment week (i.e. responders) with those who did not or who achieved a meaningful change but lapsed (i.e. nonresponders). Results During treatment, 46% of participants achieved a clinically meaningful decrease in pain intensity, and 66% achieved a clinically significant increase in number of steps per day. A total of 54% of patients were classified as responders in terms of decreases in pain intensity, and 70% were responders in terms of increases in step count. Survival analyses found that 50% of responders first achieved a clinically meaningful change by week 4 for pain intensity and week 2 for daily steps. Dropout and demographic variables were unrelated to responder status, and there was low agreement between the two measures of treatment response. Conclusions Collectively, results suggest that most responders improve within 4 weeks. Evaluating treatment response is highly specific to the outcome measure, with little correlation across outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic pain and problematic substance use are commonly cooccurring and highly detrimental issues that are especially prevalent in U.S. veteran populations. Although COVID-19 made clinical management of these conditions potentially difficult, some research suggests that certain veterans with these conditions did not experience this period as negatively as others. It is thus important to consider whether resilience factors, such as the increasinglystudied process of psychological flexibility, might have led to better outcomes for veterans managing pain and problematic substance use during this time of global crisis. Methods: This planned sub-analysis of a larger cross-sectional, anonymous, and nationally-distributed survey (N = 409) was collected during the first year of the COVID-19 pandemic. Veteran participants completed a short screener and battery of online surveys assessing pain severity and interference, substance use, psychological flexibility, mental health functioning, and pandemic-related quality of life. Results: For veterans with chronic pain and problematic substance use, the pandemic resulted in a significant lowering of their quality of life related to meeting basic needs, emotional health, and physical health compared to veterans with problematic substance use but no chronic pain diagnosis. However, moderation analyses revealed that veterans with these comorbid conditions experienced less negative impacts from the pandemic on quality of life and mental health when they reported greater psychological flexibility. For veterans with problematic substance use only, psychological flexibility was also related to better mental health functioning, but did not significantly correlate with their quality of life. Conclusion: Results highlight how COVID-19 differentially impacted veterans with both problematic substance use and chronic pain, such that this group reported particularly negative impacts of the pandemic on multiple areas of quality of life. However, our findings further emphasize that psychological flexibility, a modifiable resiliency process, also buffered against some of the negative impacts of the pandemic on mental health and quality of life. Given this, future research into the impact of natural crises and healthcare management should investigate how psychological flexibility can be targeted to help increase resiliency for veterans with chronic pain and problematic substance use. [ABSTRACT FROM AUTHOR]

Objective: Cognitive behavioral therapy for chronic pain (CBT‐CP) is an evidence‐based treatment for improving functioning and pain intensity for people with chronic pain with extensive evidence of effectiveness. However, there has been relatively little investigation of the factors associated with successful implementation and uptake of CBT‐CP, particularly clinician and system level factors. This formative evaluation examined barriers and facilitators to the successful implementation and uptake of CBT‐CP from the perspective of CBT‐CP clinicians and referring primary care clinicians. Methods: Qualitative interviews guided by the Consolidated Framework for Implementation Research were conducted at nine geographically diverse Veterans Affairs sites as part of a pragmatic clinical trial comparing synchronous, clinician‐delivered CBT‐CP and remotely delivered, technology‐assisted CBT‐CP. Analysis was informed by a grounded theory approach. Results: Twenty‐six clinicians (CBT‐CP clinicians = 17, primary care clinicians = 9) from nine VA medical centers participated in individual qualitative interviews conducted by telephone from April 2019 to August 2020. Four themes emerged in the qualitative interviews: (1) the complexity and variability of referral pathways across sites, (2) referring clinician's lack of knowledge about CBT‐CP, (3) referring clinician's difficulty identifying suitable candidates for CBT‐CP, and (4) preference for interventions that can be completed from home. Conclusions: This formative evaluation identified clinician and system barriers to widespread implementation of CBT‐CP and allowed for refinement of the subsequent implementation of two forms of CBT‐CP in an ongoing pragmatic trial. Identification of relative difference in barriers and facilitators in the two forms of CBT‐CP may emerge more clearly in a pragmatic trial that evaluates how treatments perform in real‐world settings and may provide important information to guide future system‐wide implementation efforts. [ABSTRACT FROM AUTHOR]

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g. race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p =.019). Increased age was associated with increased module use (p =.001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care. [ABSTRACT FROM AUTHOR]