Proteomic analysis of cerebrospinal fluid from neuropathic pain patients reveals proteins with potential role in spinal cord stimulation
(English)Manuscript (preprint) (Other academic)
Spinal cord stimulation (SCS) is a widely used mode of therapy in neuropathic pain of peripheral origin. Despite its well-established clinical use, the underlying physiological mechanisms behind the beneficial analgesic effects of SCS still remain only partially known. In this study, a proteomic approach was used to compare the protein concentration in cerebrospinal fluid (CSF) from responsive human patients (n=12). The comparison was made between samples taken during at two different timepoints. The first sample was taken when the stimulator had been off for 48 h, the second sample was taken after the stimulator had been used for three weeks. In total, 419 proteins could be identified (P<0.05) and relatively quantified using a shotgun proteomic approach based on immunoaffinity fractionation, multiplexed dimethyl labeling and reversed phase nanoliquid chromatography in combination with electrospray ionization high resolution tandem mass spectrometry. Statistical analysis (P<0.01) revealed two significantly down-regulated proteins; Co2 (P=0.0046), Ibp6 (P=0.0071) and five up-regulated proteins; Lynx1 (P=0.000048), Klk6 (P=0.00058), Angt (P=0.00057), A4 (P=0.0052) and Sap3 (P=0.0076) during the on state. Lynx1was the most significantly and consistently increased protein in all patients. Lynx1 is a modulator of the nicotinic acetylcholine receptor activity in the central nervous system previously described in mice. This study reports for the first time the possible involvement of Lynx1 in SCS-induced analgesia in humans.
Neuropathic pain, Cerebrospinal fluid, Spinal cord stimulation, Stable isotope labeling, Quantification, Proteomics, Mass spectrometry
Analytical Chemistry Neurosciences Anesthesiology and Intensive Care
Research subject Neuroscience; Analytical Chemistry
IdentifiersURN: urn:nbn:se:uu:diva-180108OAI: oai:DiVA.org:uu-180108DiVA: diva2:548157