Laurent Diop

Role of nerve growth factor in the trinitrobenzene sulfonic acid-induced colonic hypersensitivity

&NA; 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 mmHg (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.

Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat

Background and aims: Neutrophins are involved in somatic and visceral hypersensitivity. The action of nerve growth factor (NGF) on sensory neurones contributes to the development of referred colonic hypersensitivity induced by trinitrobenzene sulfonic acid (TNBS). Based on data on brain derived neurotrophic factor (BDNF) and calcitonin gene related peptide (CGRP) in pain, the aims of the present study were: (1) to investigate the involvement of BDNF and CGRP in this model of referred colonic hypersensitivity, (2) to test the effect of exogenous BDNF and CGRP on the colonic pain threshold, and (3) to investigate the relationship between BDNF, NGF, and CGRP by testing antineurotrophin antibodies or h-CGRP 8–37 (a CGRP antagonist) on bowel hypersensitivity induced by these peptides. Methods: Colonic sensitivity was assessed using a colonic distension procedure. Results: Anti-BDNF antibody and h-CGRP 8–37 reversed the induced decrease in colonic threshold (33.4 (2.1) and 40.3 (4.1) mm Hg, respectively, compared with a vehicle score of approximately 18 mm Hg; p<0.001). BDNF (1–100 ng/rat intraperitoneally) induced a significant dose dependent decrease in colonic reaction threshold in healthy rats. This effect was reversed by an anti-BDNF antibody and an anti-NGF antibody (33.4 (0.6) v 18.7 (0.7) mm Hg (p<0.001), anti-NGF v vehicle). NGF induced colonic hypersensitivity was reversed by h-CGRP 8–37 but not by the anti-BDNF antibody. Finally, antineurotrophin antibody could not reverse CGRP induced colonic hypersensitivity (at a dose of 1 µg/kg intraperitoneally). Conclusion: Systemic BDNF, NGF, and CGRP can induce visceral hypersensitivity alone and interactively. This cascade might be involved in TNBS induced referred colonic hypersensitivity in which each of these peptides is involved.