Antinerve Growth Factor Treatment Prevents Intestinal Dysmotility in Trichinella spiralis-Infected Rats
- Departments of 1Cell Biology, Physiology, and Immunology (D.T., P.V.) and 2Pharmacology (R.T., D.d.M.), Universitat Autònoma de Barcelona, Bellaterra, Spain
- Dr. Patri Vergara, Unitat de Fisiologia, Facultat de Veterinaria, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. E-mail:patri.vergara{at}uab.es
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
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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.
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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
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- Received February 20, 2002.
- Accepted April 9, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
