title: Differential expression of P2X7 receptor and IL-1β in nociceptive and neuropathic pain.
abstract: BACKGROUND
  Despite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Recently, we found that the adaptive immune system is involved in the pathophysiology of chronic nociceptive and neuropathic pain in humans. So far, data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. We therefore analyzed the P2X7R expression on peripheral blood lymphocytes and monocytes, as well as serum levels of IL-1β in patients suffering from chronic nociceptive and neuropathic pain in comparison to healthy volunteers in order to identify individuals who might benefit from a P2X7R modulating therapy.
  
  
  METHODS
  P2X7R messenger RNA (mRNA) and protein expression were determined in patients with either chronic nociceptive low back pain (CLBP) or neuropathic pain (NeP), and in healthy volunteers by quantitative real-time PCR (qPCR) and by fluorescence-assisted cell-sorting (FACS), respectively. IL-1β serum levels were measured with a multiplex cytokine assay.
  
  
  RESULTS
  Compared to healthy volunteers, P2X7R mRNA (1.6-fold, p = 0.038) and protein levels were significantly increased on monocytes (NeP: 24.6 ± 6.2, healthy volunteers: 17.0 ± 5.4; p = 0.002) and lymphocytes (NeP: 21.8 ± 6.5, healthy volunteers: 15.6 ± 5.2; p = 0.009) of patients with NeP, but not in patients with CLBP. Similarly, IL-1β serum concentrations were significantly elevated only in NeP patients (1.4-fold, p = 0.04).
  
  
  CONCLUSIONS
  A significant upregulation of P2X7R and increased IL-1β release seems to be a particular phenomenon in patients with NeP. P2X7R inhibitors may therefore represent a potential option for the treatment of this frequently intractable type of pain. German Clinical Trial Register (DRKS): Registration Trial DRKS00005954.
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Luchting
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany. Jens.Heyn@med.uni-muenchen.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Heyn
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Woehrle
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Banafscheh
authors.initials: B
authors.lastname: Rachinger-Adam
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kreth
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Ludwig C
authors.initials: LC
authors.lastname: Hinske
authors.affiliation: Department of Anesthesiology and Pain Medicine, LMU-Munich, Marchioninistrasse 15, 81377, Munich, Germany.
authors.forename: Shahnaz C
authors.initials: SC
authors.lastname: Azad
mesh_terms: D000328:Adult; D002469:Cell Separation; D059350:Chronic Pain / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000032:analysis / Q000096:biosynthesis / Q000097:blood*; D017116:Low Back Pain / Q000097:blood; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009437:Neuralgia / Q000097:blood* / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D058486:Receptors, Purinergic P2X7 / Q000032:analysis / Q000096:biosynthesis / Q000097:blood*
chemical_list: D053583:Interleukin-1beta; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7
keywords: Chronic low back pain; Il-1β; Neuroinflammation; Neuropathic pain; T cells; TH17; Treg