Clinical Translation: Pain and craving in opioid use disorder: Gaps in measurement and clinical care

Clinical Translation:
Pain and craving in opioid use disorder: Gaps in measurement and clinical care

R. Ross MacLean, PhD^1,2 and Suzanne Spinola, PhD^1,2
1. VA Connecticut Healthcare System, West Haven, CT
2. Yale University School of Medicine, New Haven, CT

The United States remains in the midst of an opioid crisis. Pain has been identified as an antecedent and consequence of opioid use disorder (OUD). Although estimated prevalence of OUD among individuals with chronic pain receiving long term opioid therapy vary considerably, recent guidelines that advocate tapering off prescription opioids stem from concerns for prescription opioid misuse and OUD. The relationship between pain and proximal factors associated with opioid use, such as opioid craving, is less understood. Importantly, reports of pain persist despite engagement in opioid agonist treatment (OAT), the first line treatment for OUD, consisting of buprenorphine or methadone. The current discussion summarizes and contextualizes a recently published review (MacLean, Spinola, Manhapra, & Sofuoglu, 2020)that highlighted a consistent relationship between pain and craving in individuals with chronic pain receiving long term opioid therapy and/or OUD. We will specifically focus on the complex relationship between pain and opioid craving, treatment considerations, and ways to improve measurement.

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Moher, Liberati, Tetzlaff, & Altman, 2009), we conducted an extensive literature search that resulted in 625 unique studies. Included manuscripts (n=16) focused on individuals diagnosed with chronic pain on long term opioid therapy and/or OUD with or without OAT that assessed both self-reported pain severity and opioid craving using appropriate measures and reported a minimum of descriptive statistics for pain and opioid craving for population(s) of interest. These were grouped by diagnostic focus: OUD (n=5), chronic pain on long term opioid therapy (n=9), or both (n=2). In general, we found a moderate positive relationship between pain severity and opioid craving that was more pronounced in studies of individuals with OUD. However, there was considerable heterogeneity in how pain and craving were assessed; this was reflected not only in use of different measures, but also the time frame (e.g., current, past 24 hours, past 7 days, etc.) of assessment.

Clinical discussions surrounding pain and opioid craving can reinforce stigma that contributes to poor treatment outcomes. For example, individuals with chronic pain may deny experiencing opioid cravings to reduce the appearance of OUD. Similarly, those with OUD may not request additional pain treatment so as not to appear drug seeking. Individuals with chronic pain and/or OUD may fear discussing these clinical topics, as the conversation may result in greater demands to attend the clinic or a reduction/removal of their prescribed pain medication. The relationship between pain and opioid craving is complex and achieving a greater understanding is complicated by the fact that they are difficult constructs to measure.  

Avoiding stigmatizing language in the assessment of opioid craving in individuals with chronic pain on long term opioid therapy is particularly challenging. For example, Wasan and colleagues reported an association between never reporting opioid craving and social desirability in individuals with chronic pain (Wasan et al., 2009). This potentially reflects the stigmatization of opioid craving and negative impact on clinical engagement. For individuals with chronic pain on long term opioid therapy, the experience of pain and subsequent motivation to take an opioid is expected during the course of treatment. When this process can be characterized as opioid craving is subject to clinical judgement, but the presence of persistent pain and clinical stability are typically present. Although phenotypically similar to OUD, these individuals may reject an OUD diagnosis because craving is primarily motivated by pain relief (i.e., not hedonic effects). Some have argued that chronic persistent opioid dependence (CPOD) may better describe this population (Manhapra, Arias, & Ballantyne, 2018). Consideration of the client’s experience of pain and craving can have implications for what treatments are likely to be effective and acceptable. These conversations should be collaborative and consider the client’s personal narrative to appropriately assess and guide effective treatment.

For individuals with OUD receiving OAT, pain is often superficially assessed and clinical trials of pain treatment for concurrent OUD are scarce. Clinicians treating individuals with co-occurring chronic pain and OUD tend to focus on one disorder at the expense of the other (Berg, Arnsten, Sacajiu, & Karasz, 2009). Most of the proposed strategies to address chronic pain in individuals with OUD are focused on pharmacological solutions and prescriber interventions (Alford, Barry, & Fiellin, 2013; Henningfield, Ashworth, Gerlach, Simone, & Schnoll, 2019), despite the growing literature that supports comprehensive and multimodal approaches to treating co-occurring OUD and chronic pain (Henningfield et al., 2019). There is a critical need to develop behavioral treatments that can be integrated into OAT clinical care. Given the provider and client demands inherent in treating OUD, chronic pain treatments should balance treatment burden with evidence-based care to increase access and engagement in individuals with OUD and chronic pain.

Additionally, both pain (May, Junghaenel, Ono, Stone, & Schneider, 2018)and opioid craving (Epstein et al., 2009)are known to be dynamic processes that can change moment to moment. As a result, asking clients to average their pain or opioid craving over a period of days or weeks may not accurately reflect the time course or relationship between pain and opioid craving. Use of surveys administered repeatedly in daily life, or ecological momentary assessment (EMA), may provide more valid measurement of pain and opioid craving compared to clinic or laboratory assessment. Responses to EMA surveys can capture nuanced, context-dependent changes in both pain and opioid craving that shed light on important precursors that could inform treatment.

Recent perspectives on pain treatment have included increased advocacy for clinicians to embrace the complexity of chronic pain and to develop a system of interventions that offer the promise of more effective treatment (Darnall, 2018). The incorporation of regular, thoughtful assessment of both pain and opioid craving will inform collaborative clinical decision making as well as the development of novel treatments to improve quality of life in patients with OUD and/or chronic pain.  

References: 

Alford, D., Barry, D., & Fiellin, D. (2013). Treating Pain in Patients Receiving Methadone Maintenance for Opioid Dependence. In R. Cruciani & H. Knotkova (Eds.), Handbook of Methadone Prescribing and Bupenorphine Therapy. New York, NY: Springer.

Berg, K. M., Arnsten, J. H., Sacajiu, G., & Karasz, A. (2009). Providers' experiences treating chronic pain among opioid-dependent drug users. J Gen Intern Med, 24(4), 482-488. doi:10.1007/s11606-009-0908-x

Darnall, B. (2018). To treat pain, study people in all their complexity. Nature, 557(7703), 7. doi:10.1038/d41586-018-04994-5

Epstein, D. H., Willner-Reid, J., Vahabzadeh, M., Mezghanni, M., Lin, J. L., & Preston, K. L. (2009). Real-time electronic diary reports of cue exposure and mood in the hours before cocaine and heroin craving and use. Arch Gen Psychiatry, 66(1), 88-94. doi:10.1001/archgenpsychiatry.2008.509

Henningfield, J. E., Ashworth, J. B., Gerlach, K. K., Simone, B., & Schnoll, S. H. (2019). The nexus of opioids, pain, and addiction: Challenges and solutions. Prev Med, 105852. doi:10.1016/j.ypmed.2019.105852

MacLean, R. R., Spinola, S., Manhapra, A., & Sofuoglu, M. (2020). Systematic Review of Pain Severity and Opioid Craving in Chronic Pain and Opioid Use Disorder. Pain Med, 21(2), e146-e163. doi:10.1093/pm/pnz228

Manhapra, A., Arias, A. J., & Ballantyne, J. C. (2018). The conundrum of opioid tapering in long-term opioid therapy for chronic pain: A commentary. Subst Abus, 39(2), 152-161. doi:10.1080/08897077.2017.1381663

May, M., Junghaenel, D. U., Ono, M., Stone, A. A., & Schneider, S. (2018). Ecological Momentary Assessment Methodology in Chronic Pain Research: a Systematic Review. J Pain. doi:10.1016/j.jpain.2018.01.006

Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Bmj, 339, b2535. doi:10.1136/bmj.b2535

Wasan, A. D., Butler, S. F., Budman, S. H., Fernandez, K., Weiss, R. D., Greenfield, S. F., & Jamison, R. N. (2009). Does report of craving opioid medication predict aberrant drug behavior among chronic pain patients? Clin J Pain, 25(3), 193-198. doi:10.1097/AJP.0b013e318193a6c4

Do you have any recently published work that you wish you would have had more room in the manuscript to discuss clinical implications and applications? We would love for you all to share recently published work and give us more information about how your research findings could be useful for clinicians. Please limit responses to 1,000 words and send to dana.litt@unthsc.edu by October 1, 2020.