| First Author | Zhang ZJ | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 12 | Pages | 3019-3037 |
| PubMed ID | 30455267 | Mgi Jnum | J:269886 |
| Mgi Id | MGI:6273019 | Doi | 10.1084/jem.20180800 |
| Citation | Zhang ZJ, et al. (2018) TLR8 and its endogenous ligand miR-21 contribute to neuropathic pain in murine DRG. J Exp Med 215(12):3019-3037 |
| abstractText | Toll-like receptors (TLRs) are nucleic acid-sensing receptors and have been implicated in mediating pain and itch. Here we report that Tlr8 (-/-) mice show normal itch behaviors, but have defects in neuropathic pain induced by spinal nerve ligation (SNL) in mice. SNL increased TLR8 expression in small-diameter IB4(+) DRG neurons. Inhibition of TLR8 in the DRG attenuated SNL-induced pain hypersensitivity. Conversely, intrathecal or intradermal injection of TLR8 agonist, VTX-2337, induced TLR8-dependent pain hypersensitivity. Mechanistically, TLR8, localizing in the endosomes and lysosomes, mediated ERK activation, inflammatory mediators' production, and neuronal hyperexcitability after SNL. Notably, miR-21 was increased in DRG neurons after SNL. Intrathecal injection of miR-21 showed the similar effects as VTX-2337 and inhibition of miR-21 in the DRG attenuated neuropathic pain. The present study reveals a previously unknown role of TLR8 in the maintenance of neuropathic pain, suggesting that miR-21-TLR8 signaling may be potential new targets for drug development against this type of chronic pain. |
