Gastric pain is most often modeled using distension, chemical challenge, or both, of the stomach. Many different chemicals have been used to produce gastric damage, the most common of these employed in animal models of visceral sensory transduction being hydrochloric acid or acetic acid. Intragastric administration (using a feeding tube) of hydrochloric acid, at a concentration that will induce c-fos expression in the brainstem (0.5 M), causes writhing movements indicative of a noxious visceral insult with a peak response approximately 45 minutes after administration (18). Even so, only 42% (15 of 36) of rats that received the acid infusion responded in this way (a figure reported to be similar to the incidence of pain produced in humans following infusion of hydrochloric acid onto symptomatic peptic ulcers).
Following the publication of methods by which acetic acid could be used to produce gastric ulceration (19,20) came the development of the "kissing ulcer'' (21,22). This ulceration model involves the surgical exposure of the rat stomach (under anesthesia) and the brief (45 seconds) infusion of 60% acetic acid into a restricted area of the fundus. The animals recover, but will develop ulcers on the anterior and posterior walls of the stomach within three days (Fig. 2A) (22). Rats with kissing ulcers demonstrate a significantly enhanced visceromo-tor response to gastric distension (measured using surgically implanted EMG electrodes in the acromiotrapezius muscle; distension balloons were implanted at the same time) for two weeks after the procedure (23). This enhanced response will remain up to 60 days following injection of 20% acetic acid into the stomach wall (Fig. 2) (24).
High distension pressures alone will also produce pain-like behaviors (and EMG activity recordings from the neck muscles) in rats, the threshold of which can be increased following morphine administration (25). In a comparative study of the EMG responses seen during gastric distension from different muscles (abdominal: rectus abdominus and obliquus externus; neck: acromiotrapezius and sternomastoideus; back: spinotrapezius), the most vigorous responses were seen in the acromiotrapezius muscles (24). EMG responses are graded with the distension pressure, relatively stable, and reproducible at time points beyond, and including, three days after electrode implantation (24). Rats that experience gastric distension will rapidly learn passive avoidance behavior (they will not step down from a platform if they receive a 100 mmHg gastric distension as they do so; without the distension stimulus, they will readily step down from the platform), providing further evidence that this stimulus is painful.
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