Experimental pain in gastroenterology: a reappraisal of human studies

Abdominal pain is of frequent occurrence, even in the normal population (1), and pain is probably the most prevalent symptom in the gastroenterology clinic. Consequently, characterization of gut pain is one of the most important issues in the diagnosis and assessment of organ dysfunction, and research leading to a better insight into pain mechanisms in the gastrointestinal (GI) tract will improve the treatment of patients (2). In clinical work, characterization of pain is confounded by many other symptoms caused by the diseases, such as complaints relating to psychological, cognitive and social aspects of the illness. Moreover, many diseases are typically associated with systemic reactions such as fever and general malaise, which can be difficult to distinguish from the symptoms relating to pain. Finally, the patients are typically treated with different therapeutic interventions that may cause sedation and changes in gut motor function. All such confounders can influence the perception of pain, making its assessment in clinical studies difficult. A possible way to overcome this problem is to use experimental models, where the investigator can control the pain ‘input’ e.g., the nature, localization, intensity, frequency and duration of the stimulus, and provide reproducible measures of the ‘output’ e.g., the psychophysical, behavioural or the neurophysiological response (3, 4). Experimental models have been used in different animal species, where the investigators can study the neuronal activity in anaesthetized or spinalized animals directly, with invasive techniques or with assessment of behaviour (for review, see (5)). The neurobiology of the pain system differs, however, between the species, and this limits the interpolation of findings from animal studies to man. Moreover, pain is the net effect of complex multidimensional mechanisms that involve most parts of the central nervous system. Therefore, although nociceptive reflexes or electrophysiological recordings from selected pathways in the animal nervous system are important in basic research, the central pain mechanisms and associated complex reactions are typically suppressed, and animal experiments can only to some degree reflect the experience of clinical pain in humans. Consequently, the interest in human experimental pain studies has increased rapidly during the last decade (6), and also in gastroenterology the focus has been on developing methods for experimental induction and assessment of human pain.