| First Author | Cui H | Year | 2024 |
| Journal | iScience | Volume | 27 |
| Issue | 10 | Pages | 111027 |
| PubMed ID | 39435149 | Mgi Jnum | J:357521 |
| Mgi Id | MGI:7763403 | Doi | 10.1016/j.isci.2024.111027 |
| Citation | Cui H, et al. (2024) TLR2/NF-kappaB signaling in macrophage/microglia mediated COVID-pain induced by SARS-CoV-2 envelope protein. iScience 27(10):111027 |
| abstractText | Pain has become a major symptom of long COVID-19 without effective therapy. Apart from viral infection pathological process, SARS-CoV-2 membranal proteins (envelope [S2E], spike [S2S] and membrane [S2M]) also present pro-inflammatory feature independently. Here, we aim to uncover the neuroinflammatory mechanism of COVID-pain induced by SARS-CoV-2 membranal proteins. We detected the three proteins in both peripheral sensory ganglions and spinal dorsal horn of COVID-19 donors. After intradermal and intrathecal injection, only S2E triggered pain behaviors, accompanied with upregulated-phosphorylation nuclear factor kappa B (NF-kappaB), which was significantly attenuated by minocycline in mice. We further identified Toll-like receptor 2 (TLR2) among TLRs as the target of S2E to evoke inflammatory responses leading to COVID-pain. This study identified the nociceptive effect of S2E through directly interacting with macrophage/microglia TLR2 and inducing the following NF-kappaB inflammatory storm. Clearing away S2E and inhibiting macrophage/microglia TLR2 served as perspective therapeutic strategies for COVID-19 pain. |
