Visceral and somatic hypersensitivity in a subset of rats following TNBS-induced colitis

Abstract

Background: Chronic abdominal pain is one of the most common gastrointestinal symptoms experienced by patients. Visceral hypersensitivity has been shown to be a biological marker in many patients with chronic visceral pain. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hyperalgesia of the hand/foot.

Objective: The objective of the current study was to develop an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic trinitrobenzene sulfonic acid.

Design: Male Sprague-Dawley rats (200-250g) were treated with either 20mg/rat trinitrobenzene sulfonic acid (TNBS, Sigma Chemical Co.) in 50% ethanol (n=75), an equivalent volume of 50% ethanol (n=20) or an equivalent volume of saline (n=20). The agents were delivered with a 24-gauge catheter inserted into the lumen of the colon. Mechanical and thermal behavioral tests were performed using an automated von Frey and Hargreaves device to evaluate somatic hyperalgesia. Colonic distension was performed using an automated distension device to evaluate visceral pain thresholds. All animals were tested 16weeks after TNBS treatment following complete resolution of the colitis.

Results: At 16weeks, 24% of the treated rats (18/75 rats) still exhibited evidence of visceral as well as somatic hypersensitivity compared to saline- and ethanol-treated rats.

Conclusion: Transient colonic inflammation leads to chronic visceral and somatic hypersensitivity in a subset of rats. These findings are similar to the subset of patients who develop chronic gastrointestinal symptoms following enteric infection.

Fig. 1

Colonic distension pressures that elicited the nociceptive threshold for each rat. The black squares represent saline controls and the black circles represent the ethanol-treated animals. The TNBS treated animals that recovered without any hypersensitivity are shown as black triangles and the hypersensitive rats are shown as red triangles. All values are means ± standard deviation (see Table 1). The dotted line on the y-axis = 25 mmHg.

Fig. 2

Mechanical stimulation threshold (g) that elicited hind-paw withdrawal. The black squares represent saline controls and the black circles represent the ethanol-treated animals. The TNBS-treated animals that recovered without any hypersensitivity are shown as black triangles and the hypersensitive rats are shown as red triangles. All values are means ± standard deviation (see Table 1). The dotted line on the y-axis = 18 g.

Fig. 3

Thermal stimulation threshold latency (s) that elicited hind-paw withdrawal. The black squares represent saline controls and the black circles represent the ethanol-treated animals. The TNBS-treated animals that recovered without any hypersensitivity are shown as black triangles and the hypersensitive rats are shown as red triangles. All values are means ± standard deviation (see Table 1). The dotted line on the y-axis = 8 s.

Fig. 4

Tail flick reflect threshold latency (s) that elicited tail withdrawal. The black squares represent saline controls and the black circles represent the ethanol-treated animals. The TNBS-treated animals that recovered without any hypersensitivity are shown as black triangles and the hypersensitive rats are shown as red triangles. All values are means ± standard deviation (see Table 1). The dotted line on the y-axis = 3.5 s.