Article Text

Download PDFPDF
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.

  • NGF, nerve growth factor
  • TNBS, trinitrobenzene sulfonic acid
  • BDNF, brain derived neurotrophic factor
  • CGRP, calcitonin gene related peptide
  • IBS, irritable bowel syndrome
  • SP, substance P
  • BSA, bovine serum albumin
  • h-CGRP 8–37, human calcitonin gene related and peptide fragment 8–37
  • neurotrophins
  • neuropeptides
  • irritable bowel syndrome
  • colonic distension
  • rats

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Digest
    Robin Spiller Alastair Watson