Metabolites of neuroinflammation relate to neuropathic pain after spinal cord injury

Neurology. 2020 Jun 26;10.1212/WNL.0000000000010003. doi: 10.1212/WNL.0000000000010003. Online ahead of print.


Objective: To determine whether cervical cord levels of metabolites are associated with pain sensation after spinal cord injury (SCI), we performed magnetic resonance spectroscopy in SCI patients with and without neuropathic pain (NP).

Methods: Cervical cord single-voxel spectroscopic data of 24 SCI patients (14 with NP, 10 pain-free) and 21 healthy controls were acquired at C2/3 to investigate metabolite ratios associated with neuroinflammation (choline-containing compounds to myo-inositol (tCho/mI)) and neurodegeneration (total N-acetylaspartate to myo-inositol (tNAA/mI)). NP levels were measured and Spearman's correlation tests assessed associations between metabolite levels, cord atrophy, and pin-prick score.

Results: In patients with NP, tCho/mI levels were increased (p=0.024) compared to pain-free patients and negatively related to cord atrophy (p=0.006, r=0.714). Better pin-prick score was associated with higher tCho/mI levels (p=0.032, r=0.574). In pain-free patients, tCho/mI levels were not related to cord atrophy (p=0.881, r=0.055) or pin-prick score (p=0.676, r=0.152). tNAA/mI levels were similar in both patient groups (p=0.396) and were not associated with pin-prick score in patients with NP (p=0.405, r=0.242) and pain-free patients (p=0.117, r=0.527).

Conclusions: Neuroinflammatory metabolite levels (i.e. tCho/mI) were elevated in patients with NP; its magnitude being associated with less cord atrophy and greater pain sensation (e.g. pin-prick score). This suggests that patients with NP have more residual spinal tissue and greater metabolite turnover than pain-free patients. Neurodegenerative metabolite levels (i.e. tNAA/mI) were associated with greater cord atrophy, but unrelated to NP. Identifying the metabolic NP signature provides new NP treatment targets and could improve patient stratification in interventional trials.

Classification of evidence: This study provides Class II evidence that levels of MR-spectroscopy-identified metabolites of neuroinflammation were elevated in SCI patients with NP compared to those without NP.