Effect of intrathecal nocistatin on the formalin-induced pain in mice versus that of nociceptin/orphanin FQ.
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 1 to 1000 pg. This aggravating effect of Noc/OFQ was completely reversed by 10 pg of nocistatin. At 0.3 and 1 microg, Noc/OFQ, but not nocistatin, significantly inhibited both phases of the 2% formalin-induced pain. Suppressive effects of 1 microg of Noc/OFQ on the formalin-induced pain were not affected by 1 microg 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.
Nakano
H
H
Department of Anesthesiology, Osaka Medical College, Takatsuki, Japan.
Minami
T
T
Abe
K
K
Arai
T
T
Tokumura
M
M
Ibii
N
N
Okuda-Ashitaka
E
E
Mori
H
H
Ito
S
S
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005528:Foot / Q000473:pathology; D005557:Formaldehyde; D006614:Hindlimb / Q000187:drug effects; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D010147:Pain Measurement; D013116:Spinal Cord / Q000187:drug effects; D000097629:Nociceptin
D005557:Formaldehyde; D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D000097629:Nociceptin; C111148:nocistatin