Chronic Pain Treatment With Opioid Analgesics

Benefits versus Harms of Long-term Therapy

Nalini Sehgal; James Colson; Howard S Smith


Expert Rev Neurother. 2013;13(11):1201-1220. 

In This Article

Abstract and Introduction


Chronic non-cancer pain (CNCP) is a disabling chronic condition with a high prevalence rate around the world. Opioids are routinely prescribed for treatment of chronic pain (CP). In the past two decades there has been a massive increase in the number of opioid prescriptions, prescribed daily opioid doses and overall opioid availability. Many more patients with CNCP receive high doses of long-acting opioids on a long-term basis. Yet CP and related disability rates remain high, and majority of the patients with CNCP are dissatisfied with their treatments. Intersecting with the upward trajectory in opioid use are the increasing trends in opioid related adverse effects, especially prescription drug abuse, addiction and overdose deaths. This complex situation raises questions on the relevance of opioid therapy in the treatment of CNCP. This article reviews current evidence on opioid effectiveness, the benefits and harms of long-term therapy in CNCP.


Chronic pain (CP) is defined as 'pain that persists past the normal time of healing and lasts for 3 months or longer'.[1] It is a global health problem. A WHO survey of countries in North America, South America, Europe, Middle East, Asia and Africa found the prevalence of CP to be 37.3% in developed countries and 41.1% in developing countries.[2] Different population health surveys show the prevalence of CP varies from 10.8% in Hong Kong to 60.4% in Ukraine.[2–9] Women, elderly, unemployed, less educated and obese individuals are the most vulnerable.[4–6] Pain lasts for months to years in many cases, as seen in surveys from Europe where as many as 59% individuals reported being in pain for 2–15 years.[5,10] CP is associated with poor self-rated physical and mental health, increased risk of missing work or being unemployed and greater rate of health services utilization.[4–6,9–12] The mechanisms that cause and perpetuate CP are heterogeneous, complex and not completely understood. In the vast majority, cure is not possible and treatment is directed only at symptom control and improving physical and mental well-being. The annual US costs related to pain (direct and indirect) are higher than those for cancer, heart disease and diabetes combined, and yet a large number of Americans report suboptimal pain relief.[13] European health surveys reveal that approximately 30–40% individuals with CP experience inadequate pain relief, and report high rates of dissatisfaction with their treatments.[6,14]

Opioids are used frequently to treat CP, and in the past two decades opioid use has increased dramatically. An exponential rise in the number of opioid prescriptions and the quantity (dose)[15] prescribed per patient, has been reported.[6,16–22] Opioid use in chronic non-cancer pain (CNCP) increased by >600% in Denmark in just two decades.[6] Two large health plans in the USA, serving over 1% of the US population, reported a significant increase in the use of long-term opioids between 1997 and 2005, and found that both incident and prevalent long-term opioid use had doubled in this time.[17] A significant cumulative yearly increase in morphine milligram equivalents (ME) prescribed to injured workers in Louisiana (USA) with acute pain (55 mg increase/year), and chronic pain (461 mg increase/year) was seen for claims open from 1999 and 2009.[23] In Ohio, 10% of workers compensation claims (2008–2009) involved relatively high MED exceeding 120 mg/day.[24] Opioid use trends from 1990–1996 showed increased medical use of morphine (59%), fentanyl (1168%), oxycodone (23%), hydromorphone (19%); and 6.6% increase in opioid related drug abuse rates in the USA.[18] A follow-up study from 1997–2002 showed a sharp increase in this trend oxycodone use (402.90%) showed the greatest increase followed by fentanyl (226.68%); and drug abuse rate increased from 5.75–9.85% during the same period.[19] More recent data from Center for Disease Control and Prevention (CDC) shows that sales of opioid prescription pain relievers (OPR) in the USA quadrupled from 1999 to 2010.[25] The rate of OPR sales in 2010 was 7.1 kg/10,000 population, equivalent to 710 mg/person in the USA.[25] In Ontario (Canada), a substantial increase in the use and dose of opioids for nonmalignant pain was driven primarily by the use of long-acting oxycodone and to a lesser extent, fentanyl. Opioid prescribing rates rose by 16.2% (2003–2008) and the daily dose dispensed exceeded 200 mg morphine equivalent for almost a third (32.6%) of recipients of long-acting oxycodone.[26] In Italy opioid sales increased by 292% in the decade 2000–2010, retail sales (community pharmacies) showed 286% increase in WHO step II opioids and 575% increase in WHO step III opioids.[27] Global consumption of all opioids has increased dramatically since 1996, and although it varies by regions and countries, the Americas, Europe and Oceania regions account for the highest consumption.[28]

Many factors have contributed to the unprecedented increase in opioid use and abuse in recent years. Standard physician training that emphasizes cure, inadequate undergraduate and graduate training in pain management, heightened public and media awareness of undertreated pain, have created a complex situation in which clinicians struggle to treat pain. Some patients, especially those with mental health disorders or substance abuse disorders, exploit physician's sensitivity towards pain and increasingly demand opioids for pain relief. Pain experts have encouraged CP treatment with opioids because: of the established efficacy in controlling acute pain, surgical pain and cancer pain, clinical trials report opioids decrease pain in CNCP[29,30] and drug abuse and addiction is reported to be rare in CP.[18,31] Accordingly, opioids have been prescribed liberally with the expectations that pain will decrease and activity, mood, function and quality of life (QoL) will improve in patients with CP. It is noteworthy that patients are more likely to be treated with opioids if they have poorer function, greater distress, higher disability scores or neurologic signs.[32]

This article reviews evidence on the benefits and harms of long-term opioid therapy in CP and will discuss: pain relief with opioids, effects of opioids on functional status and QoL and adverse effects of long-term opioid use, including drug overdose and deaths, risks of drug misuse and abuse.