NOCISTATIN, A PEPTIDE THAT BLOCKS NOCICEPTIN ACTION IN PAIN TRANSMISSION

Prolonged tissue damage or injury often leads to chronic pain states s uch that noxious stimuli evoke hyperalgesia and innocuous tactile stim uli evoke pain (allodynia)(1,2), The neuropeptide nociceptin(3,4), als o known as orphanin FQ (ref. 5), is an endogenous ligand for the orpha n opioid-like receptor(6-8) which induces both hyperalgesia and allody nia when administered by injection through the theca of the spinal cor d into the subarachnoid space (that is, intrathecally)(4,9). Here we s how that the nociceptin precursor(3,10-13) contains another biological ly active peptide which we call nocistatin, Nocistatin blocks nocicept in-induced allodynia and hyperalgesia, and attenuates pain evoked by p rostaglandin E-2. It is the carboxy-terminal hexapeptide of nocistatin (Glu-Gln-Lys-Gln-Leu-Gin), which is conserved in bovine, human and mu rine species, that possesses allodynia-blocking activity, We have also isolated endogenous nocistatin from bovine brain, Furthermore, intrat hecal pretreatment with anti-nocistatin antibody decreases the thresho ld for nociceptin-induced allodynia, Although nocistatin does not bind to the nociceptin receptor, it binds to the membrane of mouse brain a nd 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.