Galectin-related protein, a key contributor, drives diabetes-associated neuropathic pain.

Summary

Using proteomics and in vivo models, the authors identify LGALSL as upregulated in CSF and ACC extracellular fluid in diabetic neuropathic pain and show that exogenous LGALSL lowers mechanical thresholds via activating ACC glutamatergic neurons. These data position LGALSL as a mechanistic driver of central sensitization in diabetes-associated neuropathic pain and a potential therapeutic target.

Key Findings

• Proteomics identified LGALSL upregulation in CSF and ACC extracellular fluid in diabetic neuropathic pain model rats.
• Exogenous LGALSL administration decreased mechanical nociceptive thresholds.
• Mechanism involves activation of glutamatergic neurons in the anterior cingulate cortex.

Clinical Implications

While preclinical, LGALSL could serve as a biomarker and therapeutic target for diabetic neuropathic pain; future work may evaluate LGALSL inhibitors or modulators and assess LGALSL levels in human CSF to stratify patients.

Limitations

• Preclinical rodent models; human validation not provided
• Incomplete mechanistic pathway delineation beyond ACC glutamatergic activation

Future Directions

Validate LGALSL in human cohorts (CSF/brain tissue), define receptor/interactors and downstream signaling, and test pharmacologic modulation of LGALSL in multiple DNP models.