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Étude de l'implication du Nerve Growth Factor et des Acid-Sensing Ion Channels dans l'hypersensibilité colique induite par le butyrate chez le rat

Julien Matricon 1
1 Pharmacologie fondamentale et clinique de la douleur
Neuro-Dol - Neuro-Dol, UdA - Université d'Auvergne - Clermont-Ferrand I, INSERM - Institut National de la Santé et de la Recherche Médicale : U766
Abstract : Irritable bowel syndrome (IBS) affects about 10% people woldwide. We used an animal model of IBS induced by butyrate which has been developed in the lab in order to decipher the mechanisms of colonic hypersensitivity (CHS) in IBS. NGF blockade with anti-NGF antibodies resulted in butyrate-induced CHS prevention, which was evaluated with colorectal distension. NGF, quantified with immunohistochemistry -IHC), was overexpressed in dorsal root ganglia (DRG) innervating the colon in butyrate rats. ASIC blockade with amiloride prevented butyrate-induced CHS. ASIC1a and ASIC1b mRNA expression evaluated with RT-PCR, was increased in DRG in butyrate rats. This increase was correlated to an increase in ASIC1A protein expression in nociceptive neurons, quantified with IHC. NGF blockade with anti-NGFantibodies prevented ASIC1A overexpression in DRG. The absence ofNGF and ASIC1A expression in the colon suggested that these molecules are involved in the pre-synaptic element rather than in colonic free endings. The study of spinal Fos expression after the stimulation of colonic fibers showed that butyrate-induced CHS was associated to a specific neuronal activation in the thoracic segments T10-T11-T12 of the spinal cord. Spinal ASIC1A blockade with PcTx1 prevented butyrate-induced CHS. ASIC1a expression, evaluated with RT-PCR and Western blot, was increased in the spinal cord of butyrate rats. As in the peripheral level, ASIC1A expression aws modulated by NGF blockade prevented the overexpression of ASIC1A mRNA and protein in the spinal cod of butyarte rats. To conclude, this work suggested that NGF and ASIC1A play a critical role in the development of visceral pain by contributing to both peripheral and central sensitization.
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https://tel.archives-ouvertes.fr/tel-00719685
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Submitted on : Friday, July 20, 2012 - 2:48:26 PM
Last modification on : Tuesday, February 23, 2021 - 1:30:07 PM
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Julien Matricon. Étude de l'implication du Nerve Growth Factor et des Acid-Sensing Ion Channels dans l'hypersensibilité colique induite par le butyrate chez le rat. Neurosciences. Université d'Auvergne - Clermont-Ferrand I; Université Blaise Pascal - Clermont-Ferrand II, 2010. Français. ⟨NNT : 2010CLF1MM25⟩. ⟨tel-00719685⟩

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