PAIN is defined as an unpleasant sensation evoked by a stimulus associated with tissue damage and leading to withdrawal. The most common cause of pain is inflammation in which tissue damage is caused by trauma or immune factors. Hyperalgesia is a decrease in the nociceptive threshold and does not per se entail tissue damage. The inherent characteristics of pain-subjectivity of the experience, unpleasantness, and tissue damage-impose limitations on systematic experimental studies of pain. In animal experiments, the subject is unable to communicate the strength of the unpleasant sensation. One has to rely on gross behavioral reactions, such as paw withdrawal, writhing, or tail flicking; vocalization has been used in some experiments. In human experimentation, one must question the validity of results from individuals volunteering to withstand pain. Furthermore, the experiments are limited in design, for obvious ethical reasons. Clinical studies are performed in populations for whom pain appears spontaneously due to a disease process or accident or is elicited in the course of treatment, such as postoperative pain. The difficulty of standardizing the stimuli in clinical studies requires fairly large series. Quantitation is based on self-reporting via rating scales (e.g., the Visual Analog Scale) or on observations of functional impairment. Measurement of consumption of analgesic medication is an alternative method for evaluating the relative strength of pain. Analgesic effects of drugs are most commonly studied via self-assessment scales or by quantifying the use of rescue medication.