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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility in Trichinella spiralis-Infected Rats

D. Torrents, R. Torres, F. de Mora and P. Vergara
Journal of Pharmacology and Experimental Therapeutics August 2002, 302 (2) 659-665; DOI: https://doi.org/10.1124/jpet.102.035287
D. Torrents
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R. Torres
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F. de Mora
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P. Vergara
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Abstract

Nerve growth factor (NGF) could be involved in the development of hyperalgesia as well as in nervous remodeling consequence of inflammation. Both dysmotility and increase of visceral sensitivity have been described in functional gastrointestinal disorders such as irritable bowel syndrome. Trichinella spiralis-infected rats show an exacerbated spontaneous motility and a significant increase of the excitatory response to cholecystokinin (CCK), both associated with a reversible inflammatory process and the hypertrophy of the muscle layers. In this study we determined the intestinal expression of NGF mRNA by polymerase chain reaction and NGF by enzyme-linked immunosorbent assay. We implanted serosal strain gauge transducers on duodenum, jejunum, and ileum of anesthetized Sprague-Dawley rats to record circular muscle contractions. The experimental protocol included the evaluation of intestinal spontaneous motor activity (SMA), the response to CCK-8, and the ascending contraction induced by electrical mucosal stimulation. This protocol was performed in healthy and infected nontreated rats, in healthy rats with an NGF antibody treatment (1.6 mg/rat i.p.), and in infected rats with the same treatment applied at 0 or 3 days postinfection. NGF and NGF mRNA levels in the bowel were increased during inflammation. Although anti-NGF treatments did not prevent or reverse inflammatory response, the treatment was effective in preventing the motor alterations induced by the T. spiralis infection, i.e., inhibited increased SMA, reversed altered response to CCK, and reversed in part exacerbated response to electrical stimulation.

Footnotes

  • This work was supported by Dirección General de Investigación en Ciencia y Tecnologı́a Grant PM98-0171 and Comissionat per a Universitats i Reserca, Generalitat de Catalunya, Grants 1999SGR-00272 and 2001SGR-00214. We are also grateful to Universitat Autònoma de Barcelona for the financial support of D. Torrents.

  • DOI: 10.1124/jpet.102.035287

  • Abbreviations:
    IBS
    irritable bowel syndrome
    SMA
    spontaneous motor activity
    CCK
    cholecystokinin
    NGF
    nerve growth factor
    ELISA
    enzyme-linked immunosorbent assay
    PI
    postinfection
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    cNT
    nontreated healthy rats
    cNGF
    healthy rats treated with polyclonal neutralizing NGF
    iNT
    nontreated infected rats
    iIgG
    infected rats treated with an unspecific IgG
    NGF0
    infected rats treated with anti-NGF 1 h before infection
    NGF3
    infected rats treated with anti-NGF on day 3 postinfection
    EMS
    electrical mucosa stimulation
    l-NNA
    Nω-nitro-l-arginine
    c/h
    contractions per hour
    NO
    nitric oxide
    Ach
    acetylcholine
    • Received February 20, 2002.
    • Accepted April 9, 2002.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 302 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 302, Issue 2
1 Aug 2002
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility in Trichinella spiralis-Infected Rats

D. Torrents, R. Torres, F. de Mora and P. Vergara
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 659-665; DOI: https://doi.org/10.1124/jpet.102.035287

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility in Trichinella spiralis-Infected Rats

D. Torrents, R. Torres, F. de Mora and P. Vergara
Journal of Pharmacology and Experimental Therapeutics August 1, 2002, 302 (2) 659-665; DOI: https://doi.org/10.1124/jpet.102.035287
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