Nocistatin, a peptide that blocks nociceptin action in pain transmission

Nature. 1998 Mar 19;392(6673):286-9. doi: 10.1038/32660.


Prolonged tissue damage or injury often leads to chronic pain states such that noxious stimuli evoke hyperalgesia and innocuous tactile stimuli evoke pain (allodynia). The neuropeptide nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid-like receptor which induces both hyperalgesia and allodynia when administered by injection through the theca of the spinal cord into the subarachnoid space (that is, intrathecally). Here we show that the nociceptin precursor contains another biologically active peptide which we call nocistatin. Nocistatin blocks nociceptin-induced allodynia and hyperalgesia, and attenuates pain evoked by prostaglandin E2. It is the carboxy-terminal hexapeptide of nocistatin (Glu-Gln-Lys-Gln-Leu-Gln), which is conserved in bovine, human and murine species, that possesses allodynia-blocking activity. We have also isolated endogenous nocistatin from bovine brain. Furthermore, intrathecal pretreatment with anti-nocistatin antibody decreases the threshold for nociceptin-induced allodynia. Although nocistatin does not bind to the nociceptin receptor, it binds to the membrane of mouse brain and of spinal cord with high affinity. Our results show that nocistatin is a new biologically active peptide produced from the same precursor as nociceptin and indicate that these two peptides may play opposite roles in pain transmission.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies / immunology
  • Brain Chemistry
  • Cattle
  • Cloning, Molecular
  • Cricetinae
  • Cricetulus
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / pharmacology
  • Humans
  • Hyperalgesia / metabolism
  • Male
  • Mice
  • Molecular Sequence Data
  • Opioid Peptides / antagonists & inhibitors*
  • Opioid Peptides / cerebrospinal fluid
  • Opioid Peptides / genetics
  • Opioid Peptides / isolation & purification
  • Opioid Peptides / pharmacology
  • Opioid Peptides / physiology*
  • Pain / metabolism*
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational
  • Rats
  • Receptors, Opioid / metabolism
  • Sequence Homology, Amino Acid
  • Spinal Cord / chemistry


  • Antibodies
  • Opioid Peptides
  • Protein Precursors
  • Receptors, Opioid
  • nocistatin
  • nociceptin
  • nociceptin receptor
  • Dinoprostone

Associated data

  • GENBANK/AB005251