43: Neuroinflammation by spinal macrophage-inducible C-type lectin activation and spinal nerve ligation

Topic: Basic Science
Subtopic: Non-specific to any diagnosis (including studies in healthy animals), Neuroimmunology

Background and Aims: The spinal nerve ligation (SNL) model induces neuropathic pain through peripheral nerve injury, leading to central sensitization and neuroinflammation. Recent evidence suggests that activation of macrophage-inducible C-type lectin (Mincle) in the spinal cord may also trigger pain hypersensitivity without peripheral nerve injury. This study compared the effects of SNL and spinal Mincle activation on pain behavior and neuroglial activation.

Methods: Pain hypersensitivity was evaluated following a single intrathecal (i.t.) injection of the Mincle ligand, trehalose-6,6'-dibehenate (TDB) at doses of 0.1 µg, 1 µg, or 10 µg (single injection, S-TDB). In a separate group, rats received repeated i.t. TDB injection (10 µg/day for two days, R-TDB) or surgery for SNL. Pain behaviors were assessed for 28 days. Spinal expression of microglia (Iba1) and astrocytes (GFAP) was analyzed via immunofluorescence in R-TDB and SNL groups.

Results: Intrathecal TDB administration at all tested doses produced significant pain hypersensitivity from day 1 to day 28, with no clear dose-dependent effects. Repeated i.t. TDB administration led to greater mechanical allodynia than S-TDB, but thermal responses were similar. Compared to SNL, R-TDB group produced a comparable pain hypersensitivity to SNL but exhibited faster activation of microglia and astrocytes.

Conclusions: Spinal Mincle receptor activation via i.t. TDB induces persistent pain hypersensitivity in the absence of peripheral nerve injury, accompanied by a more rapid neuroinflammatory response than that observed in the SNL model. These findings support Mincle activation as a potential experimental model for neuroinflammation-associated neuropathic pain.

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Presenting Author: Jeong Il Choi
Submitting Author: Jeong Il Choi

Senior Author: Jeong Il Choi

IASP 2026 Global Year theme of Neuropathic Pain: No

• Hong Beom Bae: MD, PhD - Chonnam National University Medical School and Hospital
• Hyung Gon Lee - Chonnam National University Medical School and Hospital
• Jihoon Yang - Chonnam National University Hospital, Biomedical Research Institute