Proteins with potential role in analgesic effect of spinal cord stimulation on neuropathic pain

Abstract

Abstract Aims We aimed to find proteins of relevance to the prolonged analgesic effect of spinal cord stimulation (SCS) for patients with neuropathic pain. Methods The proteomes of cerebrospinal fluid (CSF) from 14 neuropathic pain patients using spinal cord stimulation (SCS) was compared to the CSF proteomes of the same patients when not using the stimulator. Samples were analyzed by dimethyl label and label free shotgun proteomics approach. Samples were prepared by immunoaffinity fractionation and then separated by reversed phase nanoliquid chromatography coupled to an electrospray ionization source and analyzed by high resolution tandem mass spectrometry. The proteins were comparatively quantified on the peptide level and ranked based on numbers of regulated peptides. Then the dimethyl and label free analysis results were combined. In order to group proteins by function and interactions, a functional enrichment network analysis was performed using the String (Search Tool for the Retrieval of Interacting Genes/Proteins) database on all significantly differentially expressed proteins. Results We found 87 differentially expressed proteins. Network analysis showed a high level of enrichment in interactions between the proteins involved in platelet degranulation and wound healing with p-values 2.48E−11 and 4.58E−08. We also recognized two additional clusters related to complement and coagulation cascades and neuropeptides. None of these proteins have been implicated in SCS mechanism previously. Conclusions Up- and down-regulations of immunological proteins and neuropeptides may explain the prolonged relief of neuropathic pain obtained after SCS. These findings contribute a new basis for understanding of SCS analgesic mechanism in human neuropathic pain. Further verification studies of these initial findings are needed.