Loss of bhlha9 Impairs Thermotaxis and Formalin-Evoked Pain in a Sexually Dimorphic Manner

Manon Bohic (1) , Irène Marics (1) , Catarina Santos (2) , Pascale Malapert (1) , Nissim Ben-Arie , Chiara Salio , Ana Reynders (1) , Yves Le Feuvre (3) , Andrew Saurin (1) , Aziz Moqrich (1)

1 IBDM - Institut de Biologie du Développement de Marseille
2 Univ Lisbon, Ctr Quim Fis Mol, P-1049001 Lisbon, Portugal
3 CNRS - Centre National de la Recherche Scientifique

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.

Mots clés: Bhhlha9; C-LTMRs; ionotropic GABAergic signaling; sexual dimorphism

Domaines: Sciences du Vivant [q-bio]

Manon Bohic, Irène Marics, Catarina Santos, Pascale Malapert, Nissim Ben-Arie, et al.. Loss of bhlha9 Impairs Thermotaxis and Formalin-Evoked Pain in a Sexually Dimorphic Manner. Cell Reports, 2020, 30 (3), pp.602-610.e6. ⟨10.1016/j.celrep.2019.12.041⟩. ⟨hal-02464543⟩