Genetic ablation of GINIP-expressing primary sensory neurons strongly impairs Formalin-evoked pain.

Abstract

Primary sensory neurons are heterogeneous by myriad of molecular criteria. However, the functional significance of this remarkable heterogeneity is just emerging. We precedently described the GINIPneurons as a new subpopulation of non peptidergic C-fibers encompassing the free nerve ending cutaneous MRGPRDneurons and C-LTMRs. Using our recently generated ginip mouse model, we have been able to selectively ablate the GINIPneurons and assess their functional role in the somatosensation. We found that ablation of GINIPneurons affected neither the molecular contents nor the central projections of the spared neurons. GINIP-DTR mice exhibited impaired sensation to gentle mechanical stimuli applied to their hairy skin and had normal responses to noxious mechanical stimuli applied to their glabrous skin, under acute and injury-induced conditions. Importantly, loss of GINIPneurons significantly altered formalin-evoked first pain and drastically suppressed the second pain response. Given that MRGPRDneurons have been shown to be dispensable for formalin-evoked pain, our study suggest that C-LTMRs play a critical role in the modulation of formalin-evoked pain.