Elsevier

Drug and Alcohol Dependence

Volume 145, 1 December 2014, Pages 143-149
Drug and Alcohol Dependence

Co-morbid pain and opioid addiction: Long term effect of opioid maintenance on acute pain

https://doi.org/10.1016/j.drugalcdep.2014.10.010Get rights and content

Highlights

  • Compared 4 chronic pain groups-methadone for addiction, buprenorphine for addiction, opioid addiction with abstinence & opioid naïve.

  • Among those with co-morbid pain and opioid addiction, there are long-term differences in pain sensitivity.

  • These differences do not resolve with discontinuation of opioid maintenance treatment compared to opioid naïve controls.

  • Pain tolerance was better among those with prolonged abstinence compared to those on active opioid maintenance.

  • Pain tolerance may improve after prolonged opioid abstinence as length of time from last use increases.

Abstract

Introduction

Medication assisted treatment for opioid dependence alters the pain experience. This study will evaluate changes pain sensitivity and tolerance with opioid treatments; and duration of this effect after treatment cessation.

Method

120 Individuals with chronic pain were recruited in 4 groups (N = 30): 1-methadone for opioid addiction; 2-buprenorphine for opioid addiction; 3-history of opioid maintenance treatment for opioid addiction but with prolonged abstinence (M = 121 weeks; SD = 23.3); and 4-opioid naïve controls. Participants completed a psychological assessment and a cold water task including, time to first pain (sensitivity) and time to stopping the pain task (tolerance). Data analysis used survival analyses.

Results

A Kaplan–Meier–Cox survival analysis showed group differences for both pain sensitivity (log rank = 15.50; p < .001) and tolerance (log rank = 20.11; p < .001). Current or historical use of opioid maintenance resulted in differing pain sensitivity compared to opioid naïve (p's < .01). However, tolerance to pain was better among those with a history of opioid maintenance compared to active methadone patients (p < .05), with the highest tolerance found among opioid naïve control group participants (p's<.001). Correlations within the prolonged abstinent group indicated pain tolerance was significantly improved as length of opioid abstinence increased (R = .37; p < .05); but duration of abstinence did not alter sensitivity (ns).

Conclusion

Among individuals with a history of prolonged opioid maintenance, there appears to be long-term differences in pain sensitivity that do not resolve with discontinuation of opioid maintenance. Although pain sensitivity does not change, pain tolerance does improve after opioid maintenance cessation. Implications for treating co-morbid opioid addiction and pain (acute and chronic) are discussed.

Introduction

Recent years have seen increasing recognition of the critical intersection between opioid addiction and chronic (non-malignant) pain. However, despite the increased interest in this topic, there is little known about the psycho-physiological links between opioid addiction and pain and extremely few empirically validated treatments (Wachholtz et al., 2011a, Wachholtz et al., 2011b).

Approximately one half to one third of Americans experience non-malignant chronic or repeating pain (Elliott et al., 1999, Tsang et al., 2008) and opioid prescribing to treat pain is on the rise (Crum, 2006, Gilson et al., 2004). There is a simultaneous rise in reported cases of abuse, or mis-use of opioid analgesics (Compton and Volkow, 2006, Crum, 2006, Drug Abuse Warning Network, 2004) with estimates of pain-related opioid abuse/addiction up to 50% (Boscarino et al., 2011, Højsted and Sjøgren, 2007, Ives et al., 2006, Reiger et al., 1990). Boscarino et al. (2011) estimate that lifetime prevalence for opioid abuse disorders among chronic pain patients is approximately 35% across both DSM-4 (35.5%) and DSM-5 (34.9%)diagnostic criteria. Longitudinal research has provided a clear picture of the negative effects of opioid abuse (Hser et al., 2001). In a study of almost 400 patients with opioid addiction entering methadone treatment, 80% reported recent pain, and 37% of patients reported chronic pain (Rosenblum et al., 2003). Of those with pain, 65% described the pain as severe or moderately severe. Comorbid pain and addiction patients also report abusing illegal drugs, alcohol, or prescription medications to treat their pain (Brands et al., 2004, Cheatle and Gallagher, 2006). The frequency of comorbid pain and opioid addiction necessitates a better understanding of the psycho-physiological links between pain and opioid addiction, and the need to provide empirically validated treatment options.

For the purposes of this study, we will use the terms for addiction and pain as agreed upon by the Liaison Committee of Pain and Addiction. This combined working group of experts from the individual fields of pain and addiction defines addiction as “behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving” (Savage et al., 2003). The International Association for the Study of Pain defines pain as, “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage” (IASP Task Force on Taxonomy, 1994). It should also be noted that the recent release of DSMV has included new diagnostic criteria for “Opioid Use Disorder.” While this criteria was not directly used in the conceptualization or patient diagnosis for this study, the newly released diagnostic criteria should be acknowledged as providing novel diagnostic criteria and a new way to conceptualize problematic opioid use.

Opioid addiction and pain reactivity is still in the early stages of research. Even treatment with opioid maintenance for pain among those with a opioid addiction history continues to be hotly debated (Gonzalez et al., 2004), due to concerns that long-term opioid maintenance enhances hyperalgesia (Doverty et al., 2001a, Doverty et al., 2001b). Animal studies exploring potential physiological mechanisms for the hyperalgesia have ranged from genetics, to specific NMDA or glutamate pathways, to descending pathways from the brain stem and the ascending pathways in the dorsal horn of the spinal column (Angst and Clark, 2006). Even environmental effects creating associative hyperalgesia, thought to be partially moderated by NMDA receptors, have received recognition as influencing hyperalgesia (Angst and Clark, 2006). Because of concerns that patients will resume addiction behaviors if opioid analgesics are administered in response to acute pain, there is a great debate in the literature about treating acute pain with opioid analgesics for individuals with an opioid addiction history (Wachholtz et al., 2011a). There is also little recognition of how hyperalgesia affects the treatment of acute pain among patients with a history of addiction to opioids (Collins and Streltzer, 2003, Lee et al., 2011). As a result, there is a limited understanding of opioid addiction related hyperalgesia in the treatment literature, and limited awareness of the psychological and physiological aspects that inform the pain experience in individuals with a history of opioid addiction.

Psychological and medical science has an extremely limited understanding of the impact of opioid mu-agonist maintenance therapy (e.g., buprenorphine or methadone) on the emotional and physiological reactivity to pain. If we do not understand how pain differentially affects those with a history of opioid addiction, how can we begin to treat it? Some earlier work has shown that individuals using chronic opioid maintenance treatment or recently abstinent from opioids show diminished pain tolerance compared to healthy controls (Compton et al., 2001, Pud et al., 2006). However, research into how maintenance doses of opioids for individuals with co-morbid chronic pain is lacking, as is any further information as to how individuals with a co-morbid pain and opioid use react psychologically and physiologically to pain.

Opioid maintenance treatment for opioid addiction (e.g., buprenorphine or methadone) alters the pain experience among individuals with co-morbid chronic pain. The current study seeks to begin to fill this gap in the scientific literature. The purpose of this study is to evaluate differences in pain sensitivity and tolerance among individuals with co-morbid pain and opioid addiction treated with methadone, and buprenorphine; and to assess whether this effect remains after treatment cessation.

Participants engaging in opioid maintenance treatment for opioid addiction with co-morbid chronic pain will have increased pain reactivity (physiological, behavioral, and psychological) compared to those with a history of treatment for opioid addiction with chronic pain who have sustained abstinence (6+ months), but currently without opioid assisted treatment, and compared to opioid naïve controls (those with chronic pain were considered opioid naïve if they have less than one month of cumulative lifetime history of PRN opioid use and no history of opioid abuse).

Section snippets

Method

One hundred and twenty individuals with history of non-malignant chronic pain and currently rating pain over 54.3. (SD = .91) in scale 0 to 100 were recruited in 4 groups (N = 30): (1)-current methadone for opioid addiction; (2)-current buprenorphine for opioid addiction; (3)-history of opioid maintenance for opioid addiction but with current prolonged abstinence of opioids (M = 121 weeks; SD = 23.3); and (4)-opioid naïve. Participants completed a psychological assessment and a cold water pain task.

Results

The demographics and baseline assessment for the full sample and by group can be found in Table 1. The study were predominately Caucasian (84%), women (60%), and in their early 40 s (M = 42 years, SD = 11). 80% of the sample reported musculoskeletal based pain, and had a mean pain score of 54.3 (SE = .91) on the SF-36. There was no significant difference between the groups on demographic variables.

While the rating of pain level induced by the cold pressor task was not significantly different between

Discussion

Similar to previous research, individuals currently on methadone or buprenorphine maintenance for opioid addiction displayed hyperalgesic reponses to the pain task (Compton et al., 2001, Doverty et al., 2001a). What makes this study unique, is the findings related to those who have achieved prolonged abstinence in comparison to the actively maintained opioid treatment group.

All participants rated the cold water test as equally painful, therefore, the lack of differences in pain rating suggests

Role of funding source

Nothing declared.

Contributors

All authors have contributed substantially to the development and writing of this paper and all of the authors approved the submitted version of this paper.

Conflict of interest statement

No conflict declared.

Acknowledgements

This paper was funded by a NIDA grant: K23DA030397 (to AW). This research was performed according to the ethical standards of University of Massachusetts Medical School. The authors would like to thank Padma Sankaran for her work as a research assistant with this project.

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