Experimental Models of Irritable Bowel Syndrome and the Role of the Enteric Neurotransmission

Abstract

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal diseases in humans. It is characterized by visceral pain and/or discomfort, hypersensitivity and abnormal motor responses along with change in gut habits. Although the etio-pathogenesis of IBS is only partially understood, a main role has been attributed to psychosocial stress of different origin. Animal models such as neonatal maternal separation, water avoidance stress and wrap restraint stress have been developed as psychosocial stressors in the attempt to reproduce the IBS symptomatology and identify the cellular mechanisms responsible for the disease. The study of these models has led to the production of drugs potentially useful for IBS treatment. This review intends to give an overview on the results obtained with the animal models; to emphasize the role of the enteric nervous system in IBS appearance and evolution and as a possible target of drug therapies.

Keywords: corticotropin releasing factor (CRF); irritable bowel syndrome (IBS); maternal separation (MS); neurotransmitters; pain; psychosocial stress; visceral hyperalgesia; water avoidance stress (WAS); wrap restrain stress (WRS).

Figure 1

Irritable bowel syndrome (IBS) pharmacotherapy. 5-HT, 5-hydroxy tryptamine; GC-C, guanylate cyclase C; NHE, sodium-hydrogen exchanger; S2, 3 and 4, sacral nerves 2, 3 and 4. Modified from Camilleri and Ford [17].

Figure 2

(A): CRFr1 and (B): CRFr2-immunoreactivity in the myenteric and submucous plexuses of rat colon. Bar = 40 μm.

Figure 3

(A): Effect of oral administration of linaclotide (0.3, 3 or 30 microg/kg) or vehicle on acute restraint stress-induced colorectal hypersensitivity to colorectal distension (CRD). (B): Effect of acute water avoidance stress on electromyografic response (EMG) to CRD. An acute session of water avoidance stress (WAS)-induced increased EMG response 24 h later. Linaclotide at 3 microg/kg p.o. completely abolished stress-induced hyperalgesia. Modified from Eutamene et al. [76]. (A) + = p < 0.05 vs. sham-stress + vehicle animals. * = p < 0.05 vs. stressed animals treated with vehicle and (B) * = p < 0.05 significantly different from baseline, + = p < 0.05 significantly different from pre-WAS.