Plasticity of dorsal root ganglion neurons in a rat model of post-infectious gut dysfunction: potential implication of nerve growth factor

Abstract

Objective. Intestinal infections are suggested as a risk factor for the development of irritable bowel syndrome (IBS)-like visceral hypersensitivity. The mechanisms implicated might involve long-term changes in visceral afferents, with implication of nerve growth factor (NGF). We explored plastic changes in dorsal root ganglia (DRGs) receiving innervation from the gut and the potential implication of NGF in a rat model of IBS-like post-infectious gut dysfunction. Materials and methods. Rats were infected with Trichinella spiralis larvae. Thirty days post-infection, inflammatory markers, including interleukins (ILs) and mucosal mast cell infiltration (rat mast cell protease II [RMCPII]), and NGF and TrkA expression was determined in the jejunum and colon (RT-qPCR). In the same animals, morphometry (neuronal body size) and NGF content (immunofluorescence) were assessed in thoracolumbar DRG neurons. Results. In infected animals, a low-grade inflammatory-like response, characterized by up-regulated levels of RMCPII and IL-6, was observed in the jejunum and colon. TrkA expression was increased in the jejunum, whereas the colon showed a slight reduction. NGF levels remained unaltered regardless the gut region. Overall, the mean cross-sectional area of DRG neurons was increased in T. spiralis-infected animals, with a reduction in both TrkA and NGF staining. Conclusions. Results suggest that during T. spiralis infection in rats, there is a remodeling of sensory afferents that might imply a NGF-mediated mechanism. Plastic changes in sensory afferents might mediate the long-lasting functional alterations that characterize this model of IBS. Similar mechanisms might be operating in patients with post-infectious-IBS.

Key Words::

• dorsal root ganglion
• irritable bowel syndrome
• mast cells
• nerve growth factor
• Trichinella spiralis
• TrkA receptor

Acknowledgments

The authors thank A. Acosta and E. Martínez for their technical assistance. This work was supported by grant 2009SGR708 from the Generalitat de Catalunya and BFU2009-08229 and BFU2010-15401 from Ministerio de Ciencia e Innovación.

Declaration of interest: F. J. designed and performed experiments, analyzed data and wrote the paper. J.A. F.-B. designed and performed experiments. V. M. designed and performed experiments, analyzed data and wrote the paper. P. V. designed experiments and wrote the paper.