Experimental and clinical aspects of opioid tolerance, physical dependenceand addiction

Long-term administration of morphine for chronic non-malignant pain continu es to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the ana lgesic and side-effects of the drug, physical dependence (which is a pure p harmacological event) and addiction (defined as a compulsive drug-related b ehaviour). Animal studies suggest that similar mechanisms underlie toleranc e and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictiv e behaviour depends on both different endogenous mechanisms and environment al factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-maligna nt pain. However, drug addiction might develop in 'at-risk patients' and th erefore 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.