This article first reviews the evidence for and against chronic
opioid therapy. Evidence supporting the
opioid responsiveness of
chronic pain, including
neuropathic pain, includes multiple randomized trials conducted over months (up to 8 months). Observational studies are conducted for longer, and many also support
opioid analgesic efficacy. Concerns have arisen about loss of efficacy with prolonged use, possibly related to tolerance or
opioid-induced
hyperalgesia. Mechanisms of tolerance and
opioid-induced
hyperalgesia are explored. Evidence on other important outcomes such as improvement in function and quality of life is mixed, and is less convincing than evidence supporting
analgesic efficacy. It is clear from current evidence that many patients abandon chronic
opioid therapy because of the unacceptability of side effects. There are also concerns about toxicity, especially when
opioids are used in high doses for prolonged periods, related to hormonal and immune function. The issue of addiction during
opioid treatment of
chronic pain is also explored. Addiction issues present many complex questions that have not been satisfactorily answered.
Opioid treatment of
pain has been, and remains, severely hampered because of actual and legal constraints related to addiction risk.
Pain advocacy has focused on placing addiction risk into context so that addiction fears do not compromise effective treatment of
pain. On the other hand, denying addiction risk during
opioid treatment of
chronic pain has not been helpful in terms of providing physicians with the tools needed for safe chronic
opioid therapy. Here, a structured goal-directed approach to chronic
opioid treatment is suggested; this aims to select and monitor patients carefully, and wean
therapy if treatment goals are not reached. Chronic
opioid therapy for
pain has not been a universal success since it was re-established during the last two decades of the twentieth century. It is now realized that the
therapy is not as effective or as free from addiction risk as was once thought. Knowing this, many ethical dilemmas arise, especially in relation to patients' right to treatment competing with physicians' need to offer the treatment selectively. In the future, we must learn how to select patients for this
therapy who are likely to achieve improvement in
pain, function and quality of life without interference from addiction. Efforts will also be made in the laboratory to identify
opioids with lower abuse potential.