POSTOPERATIVE ANALGESIC TRIALS - SOME IMPORTANT ISSUES

The post-operative pain model is a frequently used and well validated model for analgesic trials, but the complexity of many issues is often underestimated. An important distinction can be made between explanatory and pragmatic studies. The former seek to find answers to general questions that have validity outside the particular clinical situation studied. Pragmatic studies try to find the best way to treat the specific population studied. Necessary attributes of an explanatory study comprise randomization, double-blind design, and comparison with known standards such as placebo and active drug, e.g. morphine. The placebo response is part of the therapeutic effect of all active drugs as well as of pharmacologically inactive placebo therapy. The degree of placebo response and the proportion of patients showing placebo response varies over a wide range and is dependent on the circumstances of the study. The importance of documenting assay sensitivity is emphasized. Assay sensitivity is satisfactory only if the study can detect significant differences between a test drug and a placebo, between a test drug and a standard analgesic, between two active drugs, or between different doses of an active drug. Sufficiently strong baseline pain intensity is necessary to enable discrimination between analgesic drugs of different potencies without the inclusion of large numbers of patients. When patients are assigned to receive test drugs before the baseline pain level can be established, significant problems arise with assay sensitivity and interpretation of results. The increasing use of patient-controlled analgesia as a research tool has revealed new methodological problems. Some of the necessary precautions when this technique is used for comparisons of analgesic drugs are that the drugs compared must have similar pharmacokinetics and side effect profiles. Persistent post-operative pain is a neglected but important field for prospective research. Central sensitization that evokes vicious circles of pathological pain generation is thought to be essential in the pathogenesis of persistent pain after surgery. We propose a new method for the evaluation of central sensitization around a surgical wound as a sensitive research tool for examining interventions aiming at reducing the incidence and severity of persistent post-operative pain. © 1995 Elsevier Ltd.