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

M Bohic, I Marics, C Santos, P Malapert, N Ben-Arie et al

Aix-Marseille Université, CNRS, Institut de Biologie du Développement de Marseille, Marseille, France

Cell Reports

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.

BIOSEB Instruments Used:
Cold Hot Plate Test (BIO-CHP),Von Frey Filaments (Bio-VF-M),Thermal Gradient Test (BIO-GRADIENT),Thermal Place Preference, 2 Temperatures Choice Nociception Test (BIO-T2CT)

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