Drugs or drums: what relieves postoperative pain?

The cybernetic model of analgesia is a simple servo-loop: altered sensory input--complaints--medication--temporary restoration of acceptable processing of the sensory input--return of altered sensations. Under ordinary clinical circumstances the functioning of this mechanism is masked by "noise" generated by the interaction of several persons who provide the medication and time factors prolonging the interval between the onset of complaints and the action of the medication. Demand analgesia (DA) has been designed to provide prompt pain relief under the patient's direct control. The technique turned out to be useful also for the investigation of acute pain's course. The present protocol was designed to study the precision with which patients respond to minute changes in the level of a narcotic (hydromorphone) at the target site: this was achieved by varying in a double-blind fashion the amount of narcotic delivered in response to triggering the apparatus and noting how the patient adapts the dosing interval in response to the imposed changes. Thirty-four patients were studied following extensive surgery. Observation times ranged from 16 to 75 h (median 45 h) during which 89 dose changes were initiated. While the majority of subjects adapted successfully to up to 4-fold variations in drug delivery, a sizeable minority (7/34) triggered the apparatus in response to some clue other than the amount of drug received. These non-drug responders seem to correspond to the "placebo reactors" of other therapeutic settings. Our calculations allowed the estimation of how large was the contribution of drug action and non-drug action to the overall therapeutic effect. In the drug-responsive group, the mean contribution of drug action was 78%, while among the non-drug responders this amounted to only 40%. The difference between these two figures is statistically significant (P less than 0.02), at the same time it also reveals important contributions of non-drug factors in drug responders and vice versa. Whether a subject behaves as a placebo reactor or not might depend on the circumstances rather than on innate mechanisms.