Pathological pain subtypes can be classified as either neuropathic pain, caused by a somatosensory nervous system lesion or disease, or nociplastic pain, which develops without evidence of somatosensory system damage. Since there is no gold standard for the diagnosis of pathological pain subtypes, the proper classification of individual patients is currently an unmet challenge for clinicians. While the determination of specific biomarkers for each condition by current biochemical techniques is a complex task, the use of multimolecular techniques, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), combined with artificial intelligence allows specific fingerprints for pathological pain-subtypes to be obtained, which may be useful for diagnosis. We analyzed whether the information provided by the mass spectra of serum samples of four experimental models of neuropathic and nociplastic pain combined with their functional pain outcomes could enable pathological pain subtype classification by artificial neural networks. As a result, a simple and innovative clinical decision support method has been developed that combines MALDI-TOF MS serum spectra and pain evaluation with its subsequent data analysis by artificial neural networks and allows the identification and classification of pathological pain subtypes in experimental models with a high level of specificity.

Department of Chemistry Analytical Chemistry Division Faculty of Sciences University of La Laguna 38204 San Cristóbal de La Laguna Tenerife Spain

Department of Chemistry Faculty of Science Masaryk University Kamenice 5 A14 625 00 Brno Czech Republic

Department of Chemistry Faculty of Science University of Girona 17071 Girona Catalonia Spain

Department of Histology and Embryology Faculty of Medicine Masaryk University 62500 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital 656 91 Brno Czech Republic

Research Centre for Applied Molecular Oncology Masaryk Memorial Cancer Institute 62500 Brno Czech Republic

Research Group of Clinical Anatomy Embryology and Neuroscience Department of Medical Sciences University of Girona Girona Catalonia 17003 Spain

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