Metabolomics in chronic pain research

Abstract

Background and ObjectiveMetabolomics deals with the identification and quantification of small molecules (metabolites) in biological samples. As metabolite levels can reflect normal or altered metabolic pathways, their measurement provides information to improve the understanding, diagnosis and management of diseases. Despite its immense potential, metabolomics applications to pain research have been sparse. This paper describes current metabolomics techniques, reviews published human metabolomics pain research and compares successful metabolomics research in other areas of medicine with the goal of highlighting opportunities offered by metabolomics to advance pain medicine.Databases and Data TreatmentNon‐systematic review.ResultsOur search identified 19 studies that adopted a metabolomics approach in: fibromyalgia (7), chronic widespread pain (4), other musculoskeletal pain conditions (5), neuropathic pain (1), complex regional pain syndrome (1) and pelvic pain (1). The studies used either mass spectrometry or nuclear magnetic resonance. Most are characterized by small sample sizes. Some consistency has been found for alterations in glutamate and testosterone metabolism, and metabolic imbalances caused by the gut microbiome.ConclusionsMetabolomics research in chronic pain is in its infancy. Most studies are at the pilot stage. Metabolomics research has been successful in other areas of medicine. These achievements should motivate investigators to expand metabolomics research to improve the understanding of the basic mechanisms of human pain, as well as provide tools to diagnose, predict and monitor chronic pain conditions. Metabolomics research can lead to the identification of biomarkers to support the development and testing of treatments, thereby facilitating personalized pain medicine.

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

“…The bioinformatic analysis of CSF proteins related to neuropathic pain gathered from multiple studies [ 66 ] identified three groups of proteins involved in inflammatory responses (APO A1, APO C1 [ 49 ], SERPIN F1), immune responses (ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), transthyretin (TTR), gelsolin (GSN)) and metabolic processes (albumin, prothrombin (F2)), and these were all found changed in our study. 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 ].…”

“…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 ].…”

Diagnostic Biomarkers for Upper Extremity Chronic Pain Conditions

“…12 With regard to metabolites, the synovial fluid of patients with chronic symptomatic OA have elevated levels of fructose and citrate and decreased levels of O-acetylcarnitine, N-phenylacetylglycine, methionine, ethanol, creatine, malate, ethanolamine, 3hydroxybutyrate, and hexanoylcarnitine. 10 Significantly depleted serum arginine levels were found in a separate cohort of patients with knee OA. 10 Exosomes derived from mesenchymal stem cells in patients with OA carry substances that decrease the production of inflammatory mediators, including TNF-a, IL-6, prostaglandin-E2, and nitric oxide, and increase the production of the antiinflammatory marker IL-10, in the chondrocytes.…”

“…Metabolites have been studied as potential biomarkers of chronic pain conditions. 10 Additionally, exosomesdnanosized extracellular vesicles that carry proteins, lipids, and nucleic acids important in cellular communicationdmay serve as diagnostic markers and therapeutic targets for various chronic pain conditions. 11 Patients with osteoarthritis (OA) have pain with joint movement that may occur at any stage of disease progression.…”

Reduced concentrations of vaginal metabolites involved in steroid hormone biosynthesis are associated with increased vulvar vestibular pain and vaginal muscle tenderness in provoked vestibulodynia: An exploratory metabolomics study

“…Metabolomics assessment of biological samples (e.g., biofluids, tissue) has emerged as an important precision medicine tool for drug and biomarker discovery, determining drug response phenotypes, and identifying new pathophysiological mechanisms underlying chronic disease 28 – 31 including vaginal health, 32 – 34 risk for preterm birth, 35 , 36 and chronic pain conditions including endometriosis. 37 – 39 Ultimately, metabolomics may serve as a complementary tool to existing experimental approaches that can shed further light on the role sex steroid hormone alterations in PVD.…”