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In human, digestive disorders are often associated with visceral pain. In these pathologies, visceral pain threshold is decreased indicating a visceral hypersensitivity. Pregabalin [CI-1008; S-(ϩ)-3-isobutylgaba] presents antihyperalgesic actions in inflammatory somatic pain models. This study was designed to evaluate 1) the effect of injection of TNBS into the colon on visceral pain threshold, and 2) the antihyperalgesic effect of pregabalin on TNBS-induced chronic colonic allodynia. A significant decrease in the colonic pain threshold was observed in trinitrobenzene sulfonic acid (TNBS)-treated animals (17.8 Ϯ 1.27 versus 43.4 Ϯ 1.98 mm Hg). Pregabalin (30 -200 mg/kg s.c.) and morphine (0.1-1 mg/kg s.c.) showed a dose-related inhibition of TNBS-induced colonic allodynia. Pregabalin did not inhibit the colonic inflammatory effect of TNBS. In normal conditions (control animals), morphine (0.3 mg/kg s.c.) significantly increased the colonic pain threshold, whereas pregabalin (200 mg/kg s.c.) did not modify the colonic pain threshold. Pregabalin suppressed the TNBS-induced colonic allodynia but did not modify the colonic threshold in normal conditions. The ability of pregabalin to block the chronic colonic allodynia indicates that it is effective in abnormal colonic hypersensitivity, suggesting a possible effect in chronic pain in irritable bowel syndrome.

The majority of patients with digestive disorders display visceral pain. In these troubles, visceral pain threshold is decreased, demonstrating visceral hypersensitivity. There is growing evidence that nerve growth factor (NGF) may function as a mediator of persistent pain states. This hypothesis was tested in a model of colonic hypersensitivity measured by isobaric distension in conscious rats. This study was designed to evaluate (1) the effect of exogenous NGF on colonic pain threshold, (2) the involvement of NGF in trinitrobenzene sulfonic acid (TNBS)-induced colonic hypersensitivity, by testing an anti-NGF antibody, and (3) finally the involvement of sensory nerves on NGF and TNBS effects using rats treated neonatally with capsaicin. Intra-peritoneal injection of NGF (0.1-100 ng/rat) decreased in a dose-related manner colonic pain threshold in naive rats. This effect was reversed by anti-NGF antibody (1/2000; 2 ml/kg). TNBS-induced colonic hypersensitivity was also reversed by anti-NGF antibody (1/2000; 2 ml/kg): 37.7 +/- 1.7 and 17.6 +/- 0.7 mmHg (p<0.01) for anti-NGF antibody- and vehicle-treated group, respectively. Neonatal capsaicin pre-treatment inhibited NGF- and TNBS-induced decrease in colonic pain threshold: 49.4 +/- 5.3 versus 22.3 +/- 1.6 mmHg (p<0.01) for capsaicin versus vehicle in NGF-treated rats and 39.6 +/- 3.3 versus 18.0 +/- 1.0 mm Hg (p<0.001) for capsaicin versus vehicle in TNBS-treated rats. These data suggest that the action of NGF on sensory neurons contributes to the development of visceral hypersensitivity and that anti-NGF strategy may be of some therapeutic benefits in digestive sensory disorders.

Microflora-born bacteria or probiotic strains are able to modulate host-pathogens interactions in the gut. In vivo and in vitro studies indicate that species-specific modulations of intestinal cell glycosylation may represent a simple, general and efficient mechanism to adapt the host defense toward pathogens.

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