The brain contains neuronal circuits, activation of which by electrical stimulation or environmental stress causes analgesia. Both opioid and non-opioid forms of stimulus-induced analgesia exist, and are anatomically differentiated. Several transmitters have been postulated for non-opioid stimulus-induced analgesia, N-methyl-D-aspartic acid being a particularly likely candidate. In mice there are marked gender differences in the underlying neurochemical medication of stress-induced analgesia, the development of which is sensitive to the hormonal environment during early post-natal development and which changes with age in both sexes. Mice can be bred for a high or low analgesic response to stress and there is evidence that this is determined by a single gene. Operative pain, as a stressor, inhibits natural killer (NK) cell activity and influences the propensity to develop metastases when mice are inoculated with an experimental tumour after abdominal surgery. This can be influenced by peri-operative morphine in analgesic doses.