Antinociception after both peripheral and intrathecal injection of oxotremorine is modulated by spinal nitric oxide.
The present study investigated the role of spinal nitric oxide (NO) in the antinociception induced by intraperitoneal (i.p.) and intrathecal (i.th.) injection of oxotremorine. The experiments were carried out on male Wistar rats, which had cannulas chronically implanted in the lumbar enlargement of the spinal cord. Antinociceptive effects were evaluated using a tail-flick and a paw pressure test. To raise the spinal NO level, the rats received the NO donor, 3-morpholino-sydnonimine (SIN-1, 10 and 100 microg/5 microl); to lower the NO level, the inhibitor of NO synthase, N-nitro-L-arginine methyl ester (L-NAME, 50 and 400 microg/5 microl), was administered. Both those substances were injected i.th. Systemic injections of oxotremorine (0.02 and 0.1 mg/kg) produced a significant increase in the thermal nociceptive threshold, while the mechanical threshold was affected only by the higher dose (0.1 mg/kg) of the muscarinic agonist. I.th. injections of oxotremorine (0.1 ng, 1 ng, 1 microg/5 microl) produced significant antinociception in both those tests. I.th. administration of SIN-1 in doses which themselves did not affect the nociceptive threshold antagonized both the peripheral and central oxotremorine antinociception. I.th. administration of L-NAME (50 and 400 microg/5 microl) did not change the nociceptive threshold, but dose-dependently potentiated the effects of oxotremorine injected i.p. in both tests; however, the effect of i.th. administration of oxotremorine was potentiated only in the tail-flick test. Our results demonstrate that irrespective of the way of its injection, the antinociceptive effect of oxotremorine is modulated by activity of the spinal NO. Moreover, our results further support the hypothesis that NO present in the spinal cord exerts pronociceptive effects.
Machelska
H
H
Department of Molecular Neuropharmacology, Institute of Pharmacology, Kraków, Poland.
Pavone
F
F
Capone
F
F
Przewłocka
B
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007278:Injections, Spinal; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009619:Nociceptors / Q000187:drug effects*; D010095:Oxotremorine / Q000008:administration & dosage / Q000494:pharmacology*; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; C002385:linsidomine; D010095:Oxotremorine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester