Identification of nociceptin in human cerebrospinal fluid: comparison of levels in pain and non-pain states

Abstract

We have measured plasma and cerebrospinal fluid (CSF) concentrations of nociceptin, the endogenous agonist of the orphan opioid receptor-like receptor (ORL-1). We studied two groups of ten patients presenting for elective Caesarean section (Group E) or in established labour and requiring combined spinal epidural anaesthesia for pain relief (Group L). Nociceptin was identified in all CSF samples with mean +/- SD concentrations of 52.49 +/- 34.25 and 63.39 +/- 33.26 pg/ml in groups E and L, respectively. Nociceptin was identified in 16/20 plasma samples with mean +/- SD concentrations of 7.59 +/- 21.58 and 13 73 +/- 23.79 pg/ml in groups E and L, respectively. CSF concentrations were significantly higher than plasma concentrations and there were no differences between groups E and L. These data report the first measurements of CSF nociceptin in man and show no association with the acute pain of labour.

Application of an Enzyme Immunoassay for Nociceptin (Orphanin FQ)-like Immunoreactive Substances to Determination of the Human Plasma Levels

“…The human plasma levels in our EIA from 5.0 pg/ml to 16.0 pg/ ml in the daytime were nearly equivalent to those obtained with other RIA methods. The detectable plasma levels by RIA reported previously were 7.59 pg/ml (mean) 24) and 7-13 pg/ml. 25) The recovery (> 94%) and reproducibility (CV% of inner-assay and intra-assay comparisons) of this EIA with the plasma samples were satisfactory.…”

“…In a practical clinical study, human cerebrospinal fluid and plasma nociceptin levels were investigated in pain and non-pain states. 24) Furthermore, changes in the blood nociceptin levels were analyzed quantitatively in patients with acute and chronic pain, and the nociceptin levels had a relationship with the existence of pain and its duration. 28) We have established a sensitive and specific EIA system for endogenous nociceptin in human plasma, which will be valuable for application to the clinical evaluation of pain and analgesic effects of drugs, etc.…”

The Cerebrospinal Fluid in Severe Pain Conditions : Clinical, Pharmacological and Proteomic Aspects

“…Brooks et al did not find altered CSF-nociceptin levels in labour pain [35]. Raffaeli et al did not find any statistically significant differences between CSF-nociceptin of opioid-naïve chronic pain patients (n=6) vs. controls (n=9); however, chronic pain patients on continuous intrathecal morphine treatment (n=12) had a significantly lower CSF-nociceptin than controls (n=9) [195].…”

“…animal data, a small number of candidate proteins are hypothesized to be up-or downregulated in humans, and a hypothesis-testing study is then conducted. Biomarker CSF candidates in earlier studies have included Cystatin C [75,146], nociceptin [35,195], and different neurotrophins [40,143]. SP and BE are also classical candidates, and on the basis of Paper III and other studies [3,4,138,208,238,244,245], one might perhaps hypothesize that peripheral neuropathic pain and fibromyalgia are characterized by different combined patterns of CSF-BE and CSF-SP: the former would be associated with a tendency to low CSF-BE and normal/low CSF-SP, whereas the latter would be associated with a tendency to normal CSF-BE and high CSF-SP.…”

Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

“…However, numerous studies investigating the functional role of nociceptin in physiology have failed to provide coherent view, and its exact physiological role remains to be determined [2,3] . Although N/OFQ is produced by some brain structure and peripheral neurons, it is present in the liquor and blood [4] , and recent data prove that nociceptin transcripts are expressed in human immune cells as well [5] . NOP mRNA is expressed not only in nervous system, but in immune cells and other organs including the liver [6][7][8] .…”