In previous studies16, 17 we demonstrated that the response to experimentally induced pain in man could be modified by morphine and codeine, but we were unable to show any significant effects of aspirin. In both studies, electrical stimulation of two fingers and ice‐water (cold‐pressor) stimulation of each hand were used to induce pain. Both techniques permit the direct observation of two pain response parameters, pain threshold (minimal pain) and pain tolerance (maximal stimulus intensity tolerated). A third parameter, pain sensitivity range (PSR), the difference between pain tolerance and pain threshold, can also be calculated.

In man, the polypeptides brady-kinin and kallidin, but not eledoisin, produce pain on intraperitoneal injection. None of these substances produces pain when injected subcutaneously or intramuscularly in higher concentrations. Therefore, none of these polypeptides can be considered as a universal mediator of pain.

Two methods of inducing pain experimentally in man have been investigated as possible laboratory instruments for evaluating analgesic efficiency; one uses electrical stimulation of two fingers, yielding one touch and two pain response parameters, the other, thermal stimulation of the hand by immersion in ice water, yielding three pain response parameters. Sixty paid healthy volunteers were divided into three groups of 20 each. One group received placebo in all four experimental sessions, the second received morphine twice and placebo twice, and the third received aspirin twice and placebo twice. The results indicated significant changes occurring during morphine conditions for both the pain, but not the touch, response parameters produced by electrical stimulation; and for pain tolerance and pain sensitivity range, but not for pain threshold, obtained with ice‐water stimulation. Aspirin failed to produce Significant changes in any response parameter with either technique, but in some subiects lowered the pain threshold. Some laterality differences between the dominant and nondominant hands were observed which were occasionally significant.

Twenty‐four paid healthy human volunteers participated in a study of two algesimetric methods of measuring experimental pain, one employing cutaneous electrical stimulation of two fingers with one touch and two pain response parameters, the other utilizing immersion of the hand in ice water, yielding three pain response parameters. A double‐blind balanced randomized block design was used. Both permissive and nonpermissive instructions were employed with the electrical stimulation. It was found that tolerance to experimental pain consistently increased significantly with codeine for both methods and with both sets of instructions. On the other hand, codeine exerted a smaller and only occasional significant effect on pain threshold.