Expression of the nociceptin precursor and nociceptin receptor is modulated in cancer and septic patients

Br J Anaesth. 2011 Apr;106(4):566-72. doi: 10.1093/bja/aer007. Epub 2011 Feb 14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Critical Care
  • Female
  • Gene Expression
  • Humans
  • Inflammation / blood
  • Inflammation / etiology
  • Inflammation Mediators / blood
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / blood
  • Neoplasm Proteins / genetics
  • Neoplasms / blood*
  • Neoplasms / complications
  • Nociceptin Receptor
  • Pain / blood
  • Pain / etiology
  • Protein Precursors / biosynthesis*
  • Protein Precursors / blood
  • Protein Precursors / genetics
  • RNA, Messenger / genetics
  • Receptors, Opioid / biosynthesis*
  • Receptors, Opioid / blood
  • Receptors, Opioid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sepsis / blood*
  • Sepsis / complications

Substances

  • Inflammation Mediators
  • Neoplasm Proteins
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Opioid
  • pronociceptin
  • Nociceptin Receptor
  • OPRL1 protein, human