Possible antinociceptive mechanisms of opioid receptor antagonists in the mouse formalin test.
It has been reported that opioid receptor antagonist can induce antinociception in several nociceptive tests. In the intraplantar formalin pain model, however, opioid antagonist-induced antinociception, as well as its underlying mechanism, has not been well characterized. Therefore, in the mouse formalin test, we attempted to characterize the site of action and the possible opioid receptor subtypes. We found that naltrexone (a nonselective opioid antagonist) injected intraperitoneally (i.p., 1-20 mg/kg), intrathecally (i.t., 0.1-10 microg) and intracerebroventricularly (i.c.v., 0.1-10 microg) phase. Administration of beta-funaltrexamine (beta-FNA, 10-40 mg/kg i.p., 1.25-5 microg it or i.c.v.), naltrindole (1-10 mg/kg i.p., 1.25-5 microg it or i.c.v.) and nor-binaltorphimine (nor-BNI, 1-10 mg/kg i.p., 10-40 microg it or i.c.v.), which are selective mu-, delta- and kappa-opioid antagonists, respectively, also produced antinociception during the second phase. Additionally, we examined the involvement of the descending monoaminergic systems in the naltrexone-induced antinociception in the formalin test. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT, a serotonergic neurotoxin, 20 microg i.t.), but not N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, a noradrenergic neurotoxin, 20 microg i.t.), reversed the naltrexone-induced antinociception during the second phase. Our results suggest that blockade of supraspinally or spinally located opioid receptors may play roles in the regulation of antinociception during the tonic painful stage. In addition, opioid receptors localized at the neuroterminal of the descending serotonergic, but not noradrenergic, inhibitory system in the spinal cord appear to be involved in opioid antagonist-induced antinociception during the second tonic phase of the formalin test.
Choi
Seong-Soo
SS
Department of Pharmacology, College of Medicine and Institute of Natural Medicine, Hallym University, 1 Okchundong, Chunchon, Kangwon-Do, 200-702, South Korea.
Han
Ki-Jung
KJ
Lee
Han-Kyu
HK
Han
Eun-Jung
EJ
Suh
Hong-Won
HW
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001596:Benzylamines / Q000494:pharmacology; D005557:Formaldehyde; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D001596:Benzylamines; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005557:Formaldehyde; D015116:5,7-Dihydroxytryptamine; D009271:Naltrexone; C024524:beta-funaltrexamine; C055382:naltrindole; C012102:DSP 4