Abstract 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.

Keywords Opioids . Abuse . Addiction . Aberrant drug related behavior (ADRB) . Chronic pain . Epidemiology . Neurobiology . Cellular mechanisms

Introduction

Chronic pain in the general population is highly prevalent and significantly impacts quality of life [1, 2]. Chronic pain is a major burden on patients, physicians, and society. For back pain alone, total health care expenditures in 2004 and 2005 were estimated at 85 to 100 billion dollars, respectively [3]. Opioids are among the most potent analgesics available and are the cornerstone of treatment for moderate to severe pain associated with cancer [4]. Opioids also have a recognized role in chronic noncancer pain and can decrease pain and improve function in some patients [5, 6]. Opioid therapy in chronic noncancer pain, however, remains controversial [7, 8]. Opioids are far from benign medications, and their long-term use is associated with significant side effects, including tolerance, hyperalgesia, and addiction [8-10]. Problematic opioid use, including compulsive opioid seeking and addiction, arises in some fraction of opioid-treated chronic pain patients. Herein we review the literature relevant to chronic pain and opioid addiction published over recent years. Moreover, we provide some discussion on preclinical evidence for possible mechanistic interactions between pain and addiction.

Overview

Fishbain and colleagues [11] performed a structured evidence-based review on the development of abuse/ addiction and aberrant drug-related behaviors (ADRBs) in chronic pain patients (CPPs) with nonmalignant pain on exposure to chronic opioid analgesic therapy. The objective of this review was to determine the percentage of CPPs who develop abuse/addiction and/or ADRBs on chronic opioid analgesic therapy. Sixty-seven studies were reviewed in detail and assigned to one of three subgroups depending on whether they reported 1) percentages of CPPs developing abuse/addiction, 2) developing ADRBs, or 3) percentages diagnosed with alcohol/illicit drug use as determined by urine toxicology. The analysis for each of the three groups was further analyzed into those patients who were preselected for no previous history of abuse or addiction.

For the abuse/addiction grouping, there were 24 studies (2507 CPPs) with a calculated abuse/addiction rate of 3.27%. Within this grouping for those studies that had preselected CPPs for no previous or current history of abuse/addiction, the percentage of abuse/addiction was calculated at 0.19%. For the ADRB grouping, there were 17 studies (2466 CPPs) and a calculated ADRB rate of 11.5%. Within this grouping for preselected CPPs, the percentage of ADRBs was calculated at 0.59%. In the urine toxicology grouping, there were five studies (15,442 CPPs), and 20.4% of the CPPs had no prescribed opioid in urine and/or a nonprescribed opioid in urine. For five studies (1965 CPPs), illicit drugs were found in 14.5%. This study indicates that only a small percentage of patients will develop abuse/addiction, and that this percentage can be substantially less if patients are preselected for no previous history of abuse or addiction. Although addiction is a real and potential risk of opioid therapy, these data suggest that only 0.19% of patients with no prior history of abuse or addiction will actually become addicted. The far greater risk of addiction, roughly 17 times greater, lies in those patients with a prior history of abuse and addiction. It seems prudent, therefore, to carefully screen patients prior to initiating opioid therapy. A thorough screening algorithm is tantamount to managing risk. Nonetheless, more epidemiological studies are required to assess the long-term adverse consequence of opioid therapy, including opioid addiction.

Clinical Factors Associated with Prescription Opioid Abuse

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