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We found no sex difference in baseline pain threshold or tolerance levels. When partitioned by sex and expectancy state, analgesia only occurred in males during positive expectancy states at 2, 3 and 4 h post-placebo, and at 1 and 2 h post-ibuprofen. The time course of analgesic action in males was as expected considering the pharmacokinetic profile of ibuprofen. Our study found that dosages of 800 mg of ibuprofen are ineffective in producing analgesia in women regardless of their expectations. We hypothesize that ibuprofen analgesia is produced by a combination of specific pharmacological effects and a non-specific beta endorphin-mediated placebo effect. Whatever the mechanism responsible for the analgesic response seen in males, this research re-emphasizes the importance of psychological factors in determining drug response. It also shows that these factors can differ between men and women, and thus the contribution of psychological factors on analgesia needs to be seriously re-evaluated.

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SUMMARY1. In decerebrate, unanaesthetized cats two thirds of slowly adapting mechanosensitive neurones sampled in the trigeminal nucleus oralis exhibited inhibition in response to conditioning mechanical stimulation applied beyond their excitatory receptive fields. The influence of this inhibition was examined over the response range of these neurones using controlled, reproducible natural stimulation procedures.2. The extent of the inhibition was graded according to the intensity of the conditioning stimulus. It was evoked most strongly by vibratory skin indentation which very effectively excites rapidly adapting afferent fibres. Tonic conditioning inputs associated with steady skin indentation were less effective.3. The slope of stimulus-response relationships constructed from responses to inputs from the excitatory receptive field was reduced in 42 % of trigeminal nuclear cells in the presence of afferent-induced inhibition. In the remainder the slope was unchanged. 4. There was no evidence, in the neurones subject to inhibition, of an expansion of their dynamic range defined as the range of stimulus intensities over which a neurone exhibited a graded responsiveness.5. The variability in responses of an individual neurone at a given stimulus intensity was unchanged by this inhibition.6. Analysis of the stimulus-response data using information theory statistics revealed that neurones which underwent a reduction in the slope of their stimulus-response relationship in the presence of inhibition displayed a reduced capacity for defining the intensity of skin indentation. This capacity was not modified in those neurones where the slope was unchanged by the peripherally evoked inhibition.

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