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Papers of the Week

Papers: 17 Jun 2023 - 23 Jun 2023

Basic Science

Animal Studies, Molecular/Cellular

Inflammation/Inflammatory, Psychological/Comorbidities

2023 Jun 22

Nat Commun




Editor's Pick

Galectin-3 activates spinal microglia to induce inflammatory nociception in wild type but not in mice modelling Alzheimer’s disease.


Sideris-Lampretsas G, Oggero S, Zeboudj L, Silva R, Bajpai A, Dharmalingam G, Collier DA, Malcangio M


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.