Loss of bhlha9 Impairs Thermotaxis and Formalin-Evoked Pain in a Sexually Dimorphic Manner
| Autor: | Nissim Ben-Arie, Aziz Moqrich, Pascale Malapert, Catarina Santos, Irène Marics, Yves Le Feuvre, Andrew J. Saurin, Chiara Salio, Ana Reynders, Manon Bohic |
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| Přispěvatelé: | Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Univ Lisbon, Ctr Quim Fis Mol, P-1049001 Lisbon, Portugal, Centre National de la Recherche Scientifique (CNRS), ANR-17-CE16-0020,Myochronic,Etude des mécanismes moléculaires qui sous-tendent la chronicisation de la douleur. Ce qu'une Myosine non conventionnelle nous apprend(2017) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male mice [SDV]Life Sciences [q-bio] C-LTMRs Pain Inhibitory postsynaptic potential Synaptic Transmission General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine ionotropic GABAergic signaling Interneurons Formaldehyde Ganglia Spinal medicine Basic Helix-Loop-Helix Transcription Factors Thermotaxis Animals Taxis Response Receptor Bhhlha9 lcsh:QH301-705.5 gamma-Aminobutyric Acid Mice Knockout Sex Characteristics business.industry GABAA receptor Evoked pain Sexual dimorphism Mechanoreceptor 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Gene Expression Regulation Spinal Cord sexual dimorphism Excitatory postsynaptic potential Female business bhlha9 mice thermotaxis formalin-evoked pain C-LTMRs formalin-evoked pain Neuroscience bhlha9 thermotaxis Mechanoreceptors 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2020, 30 (3), pp.602-610.e6. ⟨10.1016/j.celrep.2019.12.041⟩ Cell Reports, Vol 30, Iss 3, Pp 602-610.e6 (2020) Cell Reports, 2020, 30 (3), pp.602-610.e6. ⟨10.1016/j.celrep.2019.12.041⟩ |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.12.041⟩ |
| Popis: | Summary: C-LTMRs are known to convey affective aspects of touch and to modulate injury-induced pain in humans and mice. However, a role for these neurons in temperature sensation has been suggested, but not fully demonstrated. Here, we report that deletion of C-low-threshold mechanoreceptor (C-LTMR)-expressed bhlha9 causes impaired thermotaxis behavior and exacerbated formalin-evoked pain in male, but not female, mice. Positive modulators of GABAA receptors failed to relieve inflammatory formalin pain and failed to decrease the frequency of spontaneous excitatory post-synaptic currents (sEPSCs) selectively in bhlha9 knockout (KO) males. This could be explained by a drastic change in the GABA content of lamina II inner inhibitory interneurons contacting C-LTMR central terminals. Finally, C-LTMR-specific deep RNA sequencing revealed more genes differentially expressed in male than in female bhlha9 KO C-LTMRs. Our data consolidate the role of C-LTMRs in modulation of formalin pain and provide in vivo evidence of their role in the discriminative aspects of temperature sensation. : Bohic et al. demonstrate that mice lacking the transcription factor BHLHA9 exhibit impaired thermotaxis and formalin-evoked pain. BHLHA9 mediates these effects by modulating spinal GABAergic signaling. The data consolidate the role of C-LTRMs in pain sensation and provide in vivo evidence of C-LTRMs in the discriminative aspects of temperature sensation. Keywords: C-LTMRs, Bhhlha9, sexual dimorphism, ionotropic GABAergic signaling |
| Databáze: | OpenAIRE |
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