Anti-nociceptive responses produced by human putative counterpart of nocistatin.
b-nocistatin is a heptadecapeptide produced from bovine prepronociceptin and blocks the induction of hyperalgesia and touch-evoked pain (allodynia) by intrathecal administration of nociceptin or prostaglandin E2 (PGE2). Human prepronociceptin may generate a 30-amino acid peptide different in length from b-nocistatin. Here, we examine whether the human putative counterpart of nocistatin (h-nocistatin) possessed the same biological activities as b-nocistatin. Simultaneous intrathecal injection of h-nocistatin in mice blocked the induction of allodynia by nociceptin and PGE2 in a dose-dependent manner with ID50 values of 329 pg kg(-1) and 16.6 ng kg(-1), respectively. h-nocistatin was about 10 times less potent than b-nocistatin. h-nocistatin also attenuated the nociceptin- and PGE2-induced hyperalgesia. These results demonstrate that h-nocistatin is biologically active and may be involved in the processing of pain at the spinal level in humans.
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
T
T
Minami
E
E
Okuda-Ashitaka
Y
Y
Nishiuchi
T
T
Kimura
S
S
Tachibana
H
H
Mori
S
S
Ito
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000008:administration & dosage; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*
D000700:Analgesics; D018847:Opioid Peptides; C111148:nocistatin; D015232:Dinoprostone