title: TAFA4, a chemokine-like protein, modulates injury-induced mechanical and chemical pain hypersensitivity in mice.
abstract: C-low-threshold mechanoreceptors (C-LTMRs) are unique among C-unmyelinated primary sensory neurons. These neurons convey two opposite aspects of touch sensation: a sensation of pleasantness, and a sensation of injury-induced mechanical pain. Here, we show that TAFA4 is a specific marker of C-LTMRs. Genetic labeling in combination with electrophysiological recordings show that TAFA4+ neurons have intrinsic properties of mechano-nociceptors. TAFA4-null mice exhibit enhanced mechanical and chemical hypersensitivity following inflammation and nerve injury as well as increased excitability of spinal cord lamina IIi neurons, which could be reversed by intrathecal or bath application of recombinant TAFA4 protein. In wild-type C57/Bl6 mice, intrathecal administration of TAFA4 strongly reversed carrageenan-induced mechanical hypersensitivity, suggesting a potent analgesic role of TAFA4 in pain relief. Our data provide insights into how C-LTMR-derived TAFA4 modulates neuronal excitability and controls the threshold of somatic sensation.
authors.affiliation: Aix-Marseille-Université, CNRS, Institut de Biologie du Développement de Marseille, UMR 7288, case 907, 13288 Marseille Cedex 09, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Delfini
authors.forename: Annabelle
authors.initials: A
authors.lastname: Mantilleri
authors.forename: Stéphane
authors.initials: S
authors.lastname: Gaillard
authors.forename: Jizhe
authors.initials: J
authors.lastname: Hao
authors.forename: Ana
authors.initials: A
authors.lastname: Reynders
authors.forename: Pascale
authors.initials: P
authors.lastname: Malapert
authors.forename: Serge
authors.initials: S
authors.lastname: Alonso
authors.forename: Amaury
authors.initials: A
authors.lastname: François
authors.forename: Christian
authors.initials: C
authors.lastname: Barrere
authors.forename: Rebecca
authors.initials: R
authors.lastname: Seal
authors.forename: Marc
authors.initials: M
authors.lastname: Landry
authors.forename: Alain
authors.initials: A
authors.lastname: Eschallier
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Alloui
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourinet
authors.forename: Patrick
authors.initials: P
authors.lastname: Delmas
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Feuvre
authors.forename: Aziz
authors.initials: A
authors.lastname: Moqrich
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D013314:Stress, Mechanical
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; C000594302:TAFA4 protein, mouse; D002351:Carrageenan