title: Congenital taurine deficiency in mice is associated with reduced sensitivity to nociceptive chemical stimulation.
abstract: The amino acid taurine is required for development and functioning of the central and peripheral nervous system where it exerts osmoregulatory, neuromodulatory and anti-apoptotic actions. It is subject to cellular import by the taurine transporter slc6a6. Absence of the transporter and consequently, absence of taurine leads to several neurologic deficits and sensory losses. In a slc6a6 knock-out mouse model, consequences of congenital taurine deficiency were assessed in nociceptive sensory processes. The formalin assay, hot plate assay, and summated generator potentials in response to local nociceptive stimulation with gaseous CO2 were applied. Reduced responsiveness of slc6a6(-/-) mice to nociceptive stimulation was observed in particular to chemical nociceptive stimuli. Scl6a6 knock-out mice spent significantly less time licking the formalin injected paw and displayed smaller amplitudes of the nociceptive nasal mucosa potentials than wild-type mice (p=0.002 and 0.01 respectively). In contrast, withdrawal latencies on a hot plate did not significantly differ, suggesting that intracellular taurine deficits lead in particular to a hyposensitivity of nociceptive sensory neurons sensitive to noxious chemical stimulation. As hereditary absence of taurine affects biological processes of anatomical structure development, the altered nociceptive responses likely reflect consequences of compromised peripheral nervous system development.
authors: Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany; Fraunhofer Institute of Molecular Biology and Applied Ecology-Project Group Translational Medicine and Pharmacology (IME-TMP), Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. Electronic address: j.loetsch@em.uni-frankfurt.de.
authors: J
authors: J
authors: Lötsch
authors: Smell & Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Fetscherstr. 74, D-01307 Dresden, Germany.
authors: T
authors: T
authors: Hummel
authors: Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors: U
authors: U
authors: Warskulat
authors: Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors: O
authors: O
authors: Coste
authors: Clinic for Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University, Moorenstraße 5, D-40225 Düsseldorf, Germany.
authors: D
authors: D
authors: Häussinger
authors: Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany; Fraunhofer Institute of Molecular Biology and Applied Ecology-Project Group Translational Medicine and Pharmacology (IME-TMP), Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors: G
authors: G
authors: Geisslinger
authors: Institute of Clinical Pharmacology, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
authors: I
authors: I
authors: Tegeder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D005557:Formaldehyde / Q000009:adverse effects; D006930:Hyperalgesia / Q000235:genetics* / Q000503:physiopathology*; D008562:Membrane Glycoproteins / Q000172:deficiency*; D026901:Membrane Transport Proteins / Q000172:deficiency*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059225:Nociception / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000502:physiology*; D013268:Stimulation, Chemical; D013654:Taurine / Q000378:metabolism; D013997:Time Factors; D000099247:Taurine Transporters
chemical_list: D002245:Carbon Dioxide; D005557:Formaldehyde; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D013654:Taurine; D000099247:Taurine Transporters
keywords: HSAN; NMP; analysis of variance for repeated measures; hereditary sensory and autonomic neuropathy; knock-out model; mice; negative mucosa potential; pain; rm-ANOVA