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

Abstract

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. 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. 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. 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.