Considerable evidence now exists that exposure to an intense event, such as electric shock, a noise, or even mere physical confinement, can elicit a strong form of analgesia in humans and in animals. More recently, it has been shown that an initially neutral or "meaningless" stimulus paired with this event can subsequently acquire the ability to produce an analgesia on its own. For example, a tone which has previously been paired with an electric shock has been reported to invoke a strong form of analgesia. In many situations this analgesia appears to be mediated by the release of endorphins, the body's own morphine-like substances. In other situations, a different, non-opiate mechanism appears to be involved. As a further complication, some investigators have failed to find either of these forms of conditioned analgesia. In fact, some researchers have reported exactly the opposite-- that this pairing of stimuli leads to an increase (rather than a decrease) in pain reactivity. In the present set of experiments, Dr. Grau is exploring the variables which determine whether analgesia or hyperalgesia is produced. These studies are examining two sets of factors which influence pain reactivity. The first is a determination of how and when an opioid versus a non-opioid form of analgesia is produced. The second is examining the role of environmental factors (such as time of day, testing in the training location versus in a novel location, and whether the subjects are tested during the dark or the light portion of the light/dark cycle) in the modulation of algesia. The results of these experiments are helping to answer very fundamental questions about the nature of pain responses, and providing insight into currently existing and potential pain management regimens.
