The involvement of nitric oxide in the antinociception induced by cyclosporin A in mice.
Cyclosporin A (CsA) and other immunophilin-binding agents are known to inactivate neuronal nitric oxide synthase (nNOS). Nitric oxide (NO) is involved in the nociception at the spinal level. We evaluated the effect of acute intraperitoneal (i.p.) administration of CsA on the tail-flick response in mice and the involvement of NO and opioid receptors in this effect. CsA (5, 10, 20 and 50 mg/kg i.p.) induced a significant increase in tail-flick response. Nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine (LNNA; 10, 40 and 80 mg/kg i.p.) significantly potentiated the CsA-induced (5 mg/kg) increase in tail-flick latency (TFL). While NOS substrate L-arginine (100, 200, 400 mg/kg i.p.) inhibited the CsA-induced (20 mg/kg) antinociception completely and in a dose-dependent manner. Concomitant administration of L-NNA and L-arginine blocked the inhibition exerted by the latter on the CsA-induced antinociception. The opioid receptor antagonist naloxone (4 mg/kg i.p.) did not alter the CsA effect. These results indicate that acute administration of CsA induces an antinociceptive effect that involves the L-arginine-NO pathway but is not mediated by opioid receptors.
Homayoun
Houman
H
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Babaie
Arash
A
Gharib
Behdad
B
Etminani
Atoosa
A
Khavandgar
Simin
S
Mani
Alireza
A
Dehpour
Ahmad Reza
AR
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods
D000700:Analgesics; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D016572:Cyclosporine; D019001:Nitric Oxide Synthase