Experimental and clinical aspects of opioid tolerance, physical dependence and addiction

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.