par Yoo, Sungjae;Santos, Catarina;Reynders, Ana;Marics, Irène;Malapert, Pascale;Gaillard, Stéphane;Charron, Aude;Ugolini, Sophie;Rossignol, Rafaelle;El Khallouqi, Abderazzak;Springael, Jean-Yves 
;Parmentier, Marc ;Saurin, Andrew A.J.;Goaillard, Jean Marc;Castets, Francis;Clerc, Nadine;Moqrich, Aziz
Référence Cell reports, 37, 4, 109884
Publication Publié, 2021-10
;Parmentier, Marc ;Saurin, Andrew A.J.;Goaillard, Jean Marc;Castets, Francis;Clerc, Nadine;Moqrich, AzizRéférence Cell reports, 37, 4, 109884
Publication Publié, 2021-10
Article révisé par les pairs
| Résumé : | Pain, whether acute or persistent, is a serious medical problem worldwide. However, its management remains unsatisfactory, and new analgesic molecules are required. We show here that TAFA4 reverses inflammatory, postoperative, and spared nerve injury (SNI)-induced mechanical hypersensitivity in male and female mice. TAFA4 requires functional low-density lipoprotein receptor-related proteins (LRPs) because their inhibition by RAP (receptor-associated protein) dose-dependently abolishes its antihypersensitive actions. SNI selectively decreases A-type K+ current (IA) in spinal lamina II outer excitatory interneurons (L-IIo ExINs) and induces a concomitant increase in IA and decrease in hyperpolarization-activated current (Ih) in lamina II inner inhibitory interneurons (L-IIi InhINs). Remarkably, SNI-induced ion current alterations in both IN subtypes were rescued by TAFA4 in an LRP-dependent manner. We provide insights into the mechanism by which TAFA4 reverses injury-induced mechanical hypersensitivity by restoring normal spinal neuron activity and highlight the considerable potential of TAFA4 as a treatment for injury-induced mechanical pain. |
