| First Author | Sideris-Lampretsas G | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 3579 |
| PubMed ID | 37349313 | Mgi Jnum | J:338494 |
| Mgi Id | MGI:7492843 | Doi | 10.1038/s41467-023-39077-1 |
| Citation | Sideris-Lampretsas G, et al. (2023) Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer's disease. Nat Commun 14(1):3579 |
| abstractText | Musculoskeletal chronic pain is prevalent in individuals with Alzheimer's disease (AD); however, it remains largely untreated in these patients, raising the possibility that pain mechanisms are perturbed. Here, we utilise the TASTPM transgenic mouse model of AD with the K/BxN serum transfer model of inflammatory arthritis. We show that in male and female WT mice, inflammatory allodynia is associated with a distinct spinal cord microglial response characterised by TLR4-driven transcriptional profile and upregulation of P2Y12. Dorsal horn nociceptive afferent terminals release the TLR4 ligand galectin-3 (Gal-3), and intrathecal injection of a Gal-3 inhibitor attenuates allodynia. In contrast, TASTPM mice show reduced inflammatory allodynia, which is not affected by the Gal-3 inhibitor and correlates with the emergence of a P2Y12(-) TLR4(-) microglia subset in the dorsal horn. We suggest that sensory neuron-derived Gal-3 promotes allodynia through the TLR4-regulated release of pro-nociceptive mediators by microglia, a process that is defective in TASTPM due to the absence of TLR4 in a microglia subset. |
