title: Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients: A Proteomic Mass Spectrometric Analysis.
abstract: OBJECTIVE
  Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action.
  
  
  METHODS
  Two different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks.
  
  
  RESULTS
  Eighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3).
  
  
  CONCLUSIONS
  Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
authors: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
authors: Anne-Li
authors: AL
authors: Lind
authors: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
authors: Payam
authors: P
authors: Emami Khoonsari
authors: Department of Chemistry-BMC, Analytical Chemistry, Uppsala University, Uppsala//GE Healthcare, Sweden.
authors: Marcus
authors: M
authors: Sjödin
authors: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
authors: Lenka
authors: L
authors: Katila
authors: Department of Chemistry-BMC, Analytical Chemistry, Uppsala University, Uppsala//GE Healthcare, Sweden.
authors: Magnus
authors: M
authors: Wetterhall
authors: Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, Uppsala, Sweden.
authors: Torsten
authors: T
authors: Gordh
authors: Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, Uppsala, Sweden.
authors: Kim
authors: K
authors: Kultima
mesh_terms: D000368:Aged; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009437:Neuralgia / Q000134:cerebrospinal fluid* / Q000628:therapy*; D010147:Pain Measurement; D060066:Protein Interaction Maps; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics; D062187:Spinal Cord Stimulation / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D002556:Cerebrospinal Fluid Proteins; D011506:Proteins
keywords: Cerebrospinal fluid; mechanism of action; neuropathic pain; spinal cord stimulation