title: Do low levels of beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study.
abstract: OBJECTIVE
  Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF).
  
  
  METHODS
  Cross-sectional, comparative, observational study.
  
  
  METHODS
  Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included.
  
  
  METHODS
  Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit.
  
  
  RESULTS
  We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs  = 0.725, P < 0.001 vs. rs  = 0.574, P = 0.032).
  
  
  CONCLUSIONS
  Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers.
authors.affiliation: Rehabilitation Medicine, Department of Medicine and Health Sciences, Linköping University, Linköping, Sweden; Pain and Rehabilitation Centre, UHL, County Council of Östergötland, Linköping, Sweden.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bäckryd
authors.forename: Bijar
authors.initials: B
authors.lastname: Ghafouri
authors.forename: Britt
authors.initials: B
authors.lastname: Larsson
authors.forename: Björn
authors.initials: B
authors.lastname: Gerdle
mesh_terms: D000328:Adult; D000700:Analgesics / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D059350:Chronic Pain / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000097:blood / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000503:physiopathology; D010148:Intractable Pain / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000503:physiopathology; D010149:Postoperative Pain / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000503:physiopathology; D013373:Substance P / Q000097:blood / Q000134:cerebrospinal fluid; D001615:beta-Endorphin / Q000097:blood / Q000134:cerebrospinal fluid*
chemical_list: D000700:Analgesics; D015415:Biomarkers; D013373:Substance P; D001615:beta-Endorphin
keywords: Beta-Endorphin; Biomarker; Cerebrospinal Fluid; Neuropathic; Pain; Substance P