| First Author | Yoo S | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 4 | Pages | 109884 |
| PubMed ID | 34706225 | Mgi Jnum | J:324662 |
| Mgi Id | MGI:6881793 | Doi | 10.1016/j.celrep.2021.109884 |
| Citation | Yoo S, et al. (2021) TAFA4 relieves injury-induced mechanical hypersensitivity through LDL receptors and modulation of spinal A-type K(+) current. Cell Rep 37(4):109884 |
| abstractText | 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. |
