The study describes a behavioral paradigm, using the rat, that allows direct comparison of The study describes a behavioral paradigm, using the mt, thresholds of nociceptive responses organized at spinal and supraspinal levels, and thereby permits determination of the relative efficacy of hypoalgesic treatments on these response systems. During testing, the rat's tail flick reflex is monitored while the animal performs an operant wheel turn response to escape current applied to the tail Thresholds for tail flick and wheel turn escape are assessed by the psychophysical method of constant stimuli. This paradigm is also designed to determine whether changes in response thresholds are confounded by changes in motor performance. Part 1 of the study employs the wheel turn / tail flick paradigm to assess the relative influence of a variety of hypoalgesic treatments on spinal and supraspinal pain thresholds. The treatments chosen for study are those that have been shown in the human literature to dissociate the affective-motivational and sensory-intensity dimensions of the pain experience. These treatments include systemic administration of the narcotics morphine and fentanyl, and of the benzodiazepine diazepam. Also included is presentation of a warning signal prior to application of the noxious stimulus. It is argued that ff the dissociative effects of these treatments on the dimensions of human pain are reflected by differential increases in wheel turn and tail flick thresholds, then the animal paradigm may provide a model system for the study of human pain sensitivity. Given a viable animal model, it is hoped that information garnered from the study of underlying neural mechanisms of nociception and hypoalgesia will more readily generalize to human experimental and clinical studies. Part 2 examines the underlying mechanisms that account for the dissociative effects of narcotic analgesics. Experiments in Part 2 focus on the means by which morphine administered either intracerebrally or intrathecally differentially raise spinal and supraspinal response thresholds. In order to classify the mechanisms by which these treatments dissociate response thresholds the effects of intracerebral and/or intrathecal administration of morphine, monoamines, purines and their antagonists are examined using the wheel turn tail flick paradigm.
