title: Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients.
abstract: BACKGROUND
  A role of nociceptin and its receptor (NOP) in pain and immune function has been suggested. The hypothesis was that mRNA expression of NOP and the nociceptin precursor pre-pronociceptin (pN/OFQ) in peripheral blood cells differs in end-stage cancer patients suffering from chronic pain and septic intensive care unit (ICU) patients compared with healthy controls.
  
  
  METHODS
  Blood samples were drawn from end-stage cancer patients and septic ICU patients. Additionally, postoperative patients representing individuals with surgical stress and healthy controls were enrolled as comparative groups. NOP and pN/OFQ mRNA expression, quantified by real-time polymerase chain reaction (RT-PCR), was compared between study groups, and associated to opioid medication, pain intensities, and the inflammatory markers procalcitonin (PCT) and interleukin-6.
  
  
  RESULTS
  NOP expression was significantly higher in cancer patients [normalized ratio, median (inter-quartile range): 10.2 (7.4/17.8)], postoperative patients [8.0 (5.3/10.2)], and ICU patients [6.6 (4.2/9.5)] compared with healthy controls [4.4 (2.7/7.0); P<0.001]. Expression of pN/OFQ was lower in cancer patients [3.8 (1.9/5.9)] and ICU patients [1.9 (1.0/2.7)] but not in postoperative patients compared with healthy controls [7.2 (6.1/9.4); P<0.001]. Increased plasma PCT was associated with decreased pN/OFQ in all patient groups. In cancer patients, no association was seen with pain scores, opioid medication or duration of analgesia, and NOP or pN/OFQ mRNA.
  
  
  CONCLUSIONS
  NOP and pN/OFQ expression in peripheral blood cells was modulated in end-stage cancer and septic patients compared with healthy controls, whereas changes in postoperative patients were minor. The involvement of the NOP-pN/OFQ system in inflammation, impaired immune function, and pain has to be further elucidated.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Germany. ulrike.stamer@dkf.unibe.ch
authors.forename: U M
authors.initials: UM
authors.lastname: Stamer
authors.forename: M
authors.initials: M
authors.lastname: Book
authors.forename: C
authors.initials: C
authors.lastname: Comos
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Nauck
authors.forename: F
authors.initials: F
authors.lastname: Stüber
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003422:Critical Care; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D009369:Neoplasms / Q000097:blood* / Q000150:complications; D010146:Pain / Q000097:blood / Q000209:etiology; D011498:Protein Precursors / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011957:Receptors, Opioid / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018805:Sepsis / Q000097:blood* / Q000150:complications; D000094942:Nociceptin Receptor
chemical_list: D018836:Inflammation Mediators; D009363:Neoplasm Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011957:Receptors, Opioid; C119224:pronociceptin; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human