Nonhuman animal models

There are over 50 different models of visceral pain that have been described, but only a few have been utilized in more than one laboratory.2 The recent past has seen a development of models that approximate physiological and behavioral responses similar to that of human visceral pain. One of the earliest models, the chemically induced writhing model in rodents, is produced by injecting irritant chemicals into the peritoneal cavity. This model has found less utility with the development of other models since the intraperitoneal injections did not selectively activate specific viscera, frequently yielded false positives when used to screen potential analgesic drugs, and are ethically questionable as they are associated with a persistent stimulus from which the animal cannot escape. Current models of visceral pain are more likely to utilize mechanical (e.g. distending) stimuli of controllable duration or chemical stimuli applied directly to relevant targets, thus permitting selectivity with respect to site of stimulation.

Balloon distension of hollow organs, principally along the gastrointestinal tract, is the most widely used experimental stimulus of the viscera. As noted above, experimental balloon distension of the gastrointestinal tract in humans has been established to reproduce pathologically experienced pain in terms of intensity, quality, and the area to which the sensation is referred. Whereas distending stimuli have been established as adequate for hollow organs, occlusive, ischemic, and irritant stimuli have been tested as adequate stimuli in other organs. Because inflammation of the urinary bladder is commonly associated with reports of pain and urgency in humans, experimental models of bladder irritation, including a model of cystitis, have been developed in rodents.53 Kidney stones are undeniably painful in humans and a model of artificial ureteral calculosis has been developed in rats.54 Occlusion of blood supply to most viscera is associated with pain and ischemia/anoxia is thus considered an adequate stimulus in the viscera. Accordingly, models of coronary artery occlusion and ischemia of abdominal visceral organs have been reported.55

Visceral pain is not a unitary entity and so there is a need for more than one visceral pain model. It is difficult to equate pain due to infection of the normally sterile urinary bladder with painless colons containing a sewer of the same infective organisms. Some differences between organ systems are clearly developmental in that organs which derive from midline structures (i.e. the gut) are associated with bilateral sensations, highly generalized responses and processing bilaterally within the spinal dorsal horn. In contrast, those organs which derive from unilateral structures (i.e. kidneys, ureters) generally have lateralized sensations, more regionalized responses, and lateralized spinal processing. The use of multiple models and multiple types of noxious stimuli applied to different organ systems allow us to distinguish the generalities of visceral pain from its mechanistic specifics.

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