Glutamate Signaling in Guillain-Barré Syndrome: A Potential Biomarker of Neuropathic Pain

Guillain-Barré syndrome (GBS) is an acute immune-mediated peripheral neuropathy characterized by weakness and paralysis. Although primarily considered a motor neuropathy, pain is a frequent symptom that impacts patients’ quality of life. However, it remains underestimated and lacks specific biomarkers. Neuropathic pain is associated with increased glutamate (Glu) release in the spinal cord, activating ionotropic (NMDA and AMPA) and metabotropic receptors. Given its role in nociception, Glu represents a potential biomarker for pain in GBS. This study aimed to determine Glu levels in the cerebrospinal fluid (CSF) of patients with GBS and assess effects on extracellular Ca²⁺ influx in the nociceptive DRG-derived cell line 50B11 and primary DRG neuron cultures. Glu levels were determined in CSF from patients with GBS (CSF-GBS) and controls with non-demyelinating diseases (CSF-C) using an fluorimetric enzymatic assay. In addition, Ca²⁺ influx was assessed in differentiated 50B11 cells and primary DRG neuron cultures loaded with a calcium-sensitive fluorescent dye and imaged using an InCell Analyzer. Cells were exposed to Glu, CSF-C, or CSF-GBS with or without NMDA and AMPA receptor antagonists. Glu levels were significantly higher in CSF-GBS than in CSF-C. Additionally, CSF-GBS induced sustained Ca²⁺ influx in 50B11 cells and primary DRG neuron cultures. These findings support Glu as a potential biomarker of neuropathic pain in GBS and suggest a potential therapeutic target.