Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ

Hiroyuki Nakano, Toshiaki Minami, Kohji Abe, Tohko Arai, Miwa Tokumura, Nobuhiro Ibii, Emiko Okuda-Ashitaka, Hidemaro Mori, Seiji Ito

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44 Citations (Scopus)


The effect of intrathecal nocistatin on formalin-induced pain in mice was investigated and compared with that of nociceptin/orphanin FQ (Noc/OFQ) to get information on the functional relationship between nocistatin and Noc/OFQ in the spinal cord. Subcutaneous injection of formalin into the hindpaw induced biphasic pain behaviors. Nocistatin, 1 pg, given intrathecally 1 min before 2% formalin injection, significantly attenuated the first phase of the formalin-induced pain. Also, 10 to 1000 pg of nocistatin, given 10 min after formalin injection, significantly inhibited the second phase of the formalin test. Naloxone, 5 mg/kg i.p., failed to antagonize inhibitory effects of nocistatin on either phase of the formalin- induced pain, indicating that analgesic effects of nocistatin were unrelated to the classic opioid system. At 1 to 100 pg, Noc/OFQ exerted no influence on either phase of the 2% formalin-induced pain. However, at 1% formalin, Noc/OFQ significantly aggravated the second phase at 10 pg but not the first phase at I to 1000 pg. This aggravating effect of Noc/OFQ was completely reversed by 10 pg of nocistatin. At 0.3 and 1 μg, Noc/OFQ, but not nocistatin, significantly inhibited both phases of the 2% formalin-induced pain. Suppressive effects of 1 μg of Noc/OFQ on the formalin-induced pain were not affected by 1 μg of nocistatin. These results suggest that Noc/OFQ might be involved in the second phase of the mouse formalin test and that, under such pathophysiological conditions, nocistatin could exhibit antagonism against Noc/OFQ at the spinal level.

Original languageEnglish
Pages (from-to)331-336
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - Jan 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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