Metabolites of neuroinflammation relate to neuropathic pain after spinal cord injury

Abstract

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.

Systematic analysis of critical genes and pathways identified a signature of neuropathic pain after spinal cord injury

“…Spinal cord injury (SCI) not only causes motor dysfunction but also causes neuropathic pain (NP) that is resistant to medical treatment and severely affects the quality of life of patients (Behroozi et al, 2021; Pfyffer et al, 2020; G. Zhang & Yang, 2017). The prevalence of NP after SCI is reported to be 53% to 80% (Brown et al, 2021; Burke et al, 2017; Gruener et al, 2020; Hunt et al, 2021; Kim et al, 2020).…”

“…Spinal cord injury (SCI) not only causes motor dysfunction but also causes neuropathic pain (NP) that is resistant to medical treatment and severely affects the quality of life of patients (Behroozi et al, 2021;Pfyffer et al, 2020;G. Zhang & Yang, 2017).…”

Efficacy of transcutaneous electrical nerve stimulation in people with pain after spinal cord injury: a meta-analysis

“…A previous study investigating pain in mice with pain disorders has shown that TENS relieves nociceptive hyperalgesia and maintains spinal opioid receptors by inhibiting mitogen-activated protein kinase and proinflammatory cytokine expression to activate PKC-γ and P-CREB [ 33 ]. Moreover, Pfyffer et al [ 34 ] have revealed that TENS can excite crude fibers and activate glial cells to release inhibitory neurotransmitters. Thus, the injury sensory signals generated from the same segment of fine fibers on the spinal dorsal horn of the projected neuron’s excitatory action, are inhibited.…”

Multi-Omics Approach to Elucidate Cerebrospinal Fluid Changes in Dogs with Intervertebral Disc Herniation

“…The application of metabolomics in pain research is still at an early stage [ 67 ]. Notwithstanding this issue, the metabolomics of the CSF in pain patients revealed that neuropathic pain alters sphingomyelin–ceramide metabolism, nervous tissue damage (alanine, taurine) and inflammatory processes (choline) [ 67 , 68 , 69 ]. Choline, which was found to be elevated in IVDH dogs in our study, is a metabolite related to glial activity, and its elevation was found to be linked with worse pain interference [ 69 ].…”