title: 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 GINIP+neurons as a new subpopulation of non peptidergic C-fibers encompassing the free nerve ending cutaneous MRGPRD+neurons and C-LTMRs. Using our recently generated ginip mouse model, we have been able to selectively ablate the GINIP+neurons and assess their functional role in the somatosensation. We found that ablation of GINIP+neurons 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 GINIP+neurons significantly altered formalin-evoked first pain and drastically suppressed the second pain response. Given that MRGPRD+neurons 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.
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Louise
authors.initials: L
authors.lastname: Urien
authors.affiliation: Phenotype Expertise, 5 Boulevard du Maréchal Koenig, 13009 Marseille, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gaillard
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Lo Re
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Malapert
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Bohic
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Ana
authors.initials: A
authors.lastname: Reynders
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Aziz
authors.initials: A
authors.lastname: Moqrich
mesh_terms: D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D005557:Formaldehyde / Q000009:adverse effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005838:Genotype; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000235:genetics; D010146:Pain / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010812:Physical Stimulation; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012684:Sensory Thresholds; D013696:Temperature
chemical_list: D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D005557:Formaldehyde