B. Berthold Wolff

Response of experimental pain to analgesic drugs: I. Morphine, aspirin, and placebo

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.

EFFECT OF SUGGESTION UPON EXPERIMENTAL PAIN RESPONSE PARAMETERS

The differential effects of permissive and non-permissive instructions upon pain threshold and pain tolerance were studied in 43 healthy human Ss, using cutaneous electrical stimulation. Non-permissive instructions resulted in very significant increases in both pain tolerance and pain sensitivity range, but no significant changes were observed for both pain threshold and detection threshold. Therefore, Gelfands hypothesis, stating that pain threshold and pain tolerance have differential loadings of physiological and psychological components, was supported. It was also found that the left or non-dominant hand was consistently more sensitive to pain than the right hand. This result is consistent with Wolffs and Jarviks suggestion that lateral dominance is important in pain perception.

Response of experimental pain to analgesic drugs; III. Codeine, aspirin, secobarbital, and placebo

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.

Response of experimental pain to analgesic drugs. II. Codeine and placebo.

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.

Bradykinin as a Mediator of Human Pain.

Summary 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.