Abstract

ObjectiveTo determine whether cervical cord levels of metabolites are associated with pain sensation after spinal cord injury (SCI) by performing magnetic resonance spectroscopy in patients with SCI with and without neuropathic pain (NP).MethodsCervical cord single-voxel spectroscopic data of 24 patients with SCI (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 myoinositol [tCho/mI]) and neurodegeneration (total N-acetylaspartate to myo-inositol [tNAA/mI]). NP levels were measured, and Spearman correlation tests assessed associations between metabolite levels, cord atrophy, and pinprick score.ResultsIn 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 pinprick 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 pinprick score (p = 0.676, r = 0.152). tNAA/mI levels were similar in both patient groups (p = 0.396) and were not associated with pinprick score in patients with NP (p = 0.405, r = 0.242) and pain-free patients (p = 0.117, r = 0.527).ConclusionsNeuroinflammatory 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., pinprick 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 evidenceThis study provides Class II evidence that levels of magnetic resonance spectroscopy–identified metabolites of neuroinflammation were elevated in patients with SCI with NP compared to those without NP.

Highlights

  • Cervical cord single-voxel spectroscopic data of 24 patients with spinal cord injury (SCI) (14 with neuropathic pain (NP), 10 pain-free) and 21 healthy controls were acquired at C2/3 to investigate metabolite ratios associated with neuroinflammation and neurodegeneration

  • Neuroinflammatory metabolite levels were elevated in patients with NP, its magnitude being associated with less cord atrophy and greater pain sensation

  • Classification of evidence This study provides Class II evidence that levels of magnetic resonance spectroscopy–identified metabolites of neuroinflammation were elevated in patients with SCI with NP compared to those without NP

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Summary

Methods

Cervical cord single-voxel spectroscopic data of 24 patients with SCI (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 myoinositol [tCho/mI]) and neurodegeneration (total N-acetylaspartate to myo-inositol [tNAA/mI]). A subset (9 paraplegic patients, 9 tetraplegic patients, and 11 healthy controls) of the data of this study was previously reported to assess metabolite ratios in the cervical spinal cord after SCI.[9]. Primary research question The primary research question of this study was whether levels of metabolites of neuroinflammation assessed by cervical cord MRS are elevated in patients with SCI with NP compared to those without NP.

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