Visceral analgesic effect of 5-HT(4) receptor agonist in rats involves the rostroventral medulla (RVM).

The 5-HT(4) receptor agonist tegaserod (TEG) has been reported to modulate visceral pain. However, the underlying mechanism remains unknown. The objective of the present study was to examine the analgesic mechanism and site of action of TEG. In male rats, visceral pain was assessed by measuring visceromotor response (VMR) to colorectal distension (CRD). Inflammation was induced by intracolonic injection of tri-nitrobenzene sulfonic acid (TNBS). The effect of TEG on the VMR was tested by injecting intraperitoneal (i.p.), intrathecal (i.t.), intracerebroventricular (i.c.v) or in the rostroventral medulla (RVM). The effect of the drug was also tested on responses of CRD-sensitive pelvic nerve afferents (PNA) and lumbo-sacral (LS) spinal neurons. Systemic injection of TEG attenuated VMR in naive and TNBS-treated rats. Similarly, supraspinal, but not spinal, injection of TEG attenuated the VMR. While GR113808, (selective 5-HT(4) antagonist) blocked the effect, naloxone (NLX) an opioid receptor antagonist reversed the effect of TEG. Although i.t. NLX did not block the inhibitory effect of TEG in VMR study, i.t. injection of α2-adrenergic receptor antagonist yohimbine blocked the effect of TEG when given systemically. While TEG had no effect on the responses of CRD-sensitive PNA, it inhibited the responses of CRD-sensitive LS neurons in spinal intact condition. This inhibition was blocked by GR113808, NLX and ß-funaltrexamine (ß-FNA) when injected into the RVM. Results indicate that TEG produces analgesia via activation of supraspinal 5-HT(4) receptors which triggers the release of opioids at supraspinal site, which activates descending noradrenergic pathways to the spinal cord to produce analgesia.

Effects of Bifidobacterium infantis 35624 on post-inflammatory visceral hypersensitivity in the rat.

BACKGROUND: Irritable bowel syndrome patients have abnormal visceral perception. Probiotic organisms may produce beneficial effects in these patients by reducing visceral hypersensitivity. AIM: To investigate the effects of the probiotic organism, Bifidobacterium infantis 35624, on post-inflammatory visceral hypersensitivity in rats. METHODS: Colitis was induced using intracolonic administration of trinitrobenzenesulfonic acid; control rats received saline (day 0). Myeloperoxidase (MPO) levels and colonic damage scores were determined. From days 15-29, rats (n = 10/group) rats were orally dosed with 2 ml of B. infantis ≥ 10(8) colony-forming units/ml or vehicle (MRS broth). A second series of rats (n = 10/group) was dosed in the same manner from days 15-59. The level of colonic stimulation during colorectal distension (CRD) was determined by recording a visceromotor response (VMR) to CRD at 30 mmHg pre- and post-treatment. Post-treatment samples of colonic tissue were weighed, graded for morphologic damage, and assayed for MPO levels. RESULTS: All rats were hypersensitive at day 15. On day 30, hypersensitivity to colorectal distension remained in the vehicle group, but was significantly reduced in the B. infantis group (mean VMR/10 min: vehicle = 15.4 ± 1.0 vs. B. infantis = 7.6 ± 1.0, p < 0.001). A similar, significant effect was observed at day 60. On both day 30 and day 60, tissue weight, colonic damage scores, and MPO levels resembled those of control animals. CONCLUSIONS: Oral administration of Bifidobacterium infantis 35624 normalized sensitivity to colorectal distension in a rat model of post-inflammatory colonic hypersensitivity.