Loss of bhlha9 Impairs Thermotaxis and Formalin-Evoked Pain in a Sexually Dimorphic Manner.
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|Manon|M|', 'Marics|Irène|I|', 'Santos|Catarina|C|', 'Malapert|Pascale|P|', 'Ben-Arie|Nissim|N|', 'Salio|Chiara|C|', 'Reynders|Ana|A|', 'Le Feuvre|Yves|Y|', 'Saurin|Andrew J|AJ|', 'Moqrich|Aziz|A|']
D000818:Animals D051792:Basic Helix-Loop-Helix Transcription Factors D005260:Female D005557:Formaldehyde D005727:Ganglia, Spinal D005786:Gene Expression Regulation D007395:Interneurons D008297:Male D008465:Mechanoreceptors D018345:Mice, Knockout D010146:Pain D012727:Sex Characteristics D013116:Spinal Cord D009435:Synaptic Transmission D000071442:Taxis Response D005680:gamma-Aminobutyric Acid
sexual dimorphism C-LTMRs Bhhlha9 ionotropic GABAergic signaling