Participation of the opioid receptor - nitric oxide - cGMP - K+ channel pathway in the peripheral antinociceptive effect of nalbuphine and buprenorphine in rats.
Can J Physiol Pharmacol
; 98(11): 753-762, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-33095677
ABSTRACT
The aim of this study was to examine if the peripheral antinociceptive effects of the opioid agonist/antagonist nalbuphine and buprenorphine involve the sequential participation of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) synthesis followed by K+ channel opening in the formalin test. Wistar rats (180-220 g) were injected in the dorsal surface of the right hind paw with formalin (1%). Rats received a subcutaneous (s.c.) injection into the dorsal surface of the paw of vehicles or increasing doses of nalbuphine (50-200 µg/paw) or buprenorphine (1-5 µg/paw) 20 min before formalin injection into the paw. Nalbuphine antinociception was reversed by the s.c. injection into the paw of the inhibitor of NO synthesis (NG-nitro-l-arginine methyl ester (L-NAME)), by the inhibitor of guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ)), by the Kir6.1-2, ATP-sensitive K+ channel inhibitors (glibenclamide and glipizide), by the KCa2.1-3, small conductance Ca2+-activated K+ channel blocker (apamin), by the KCa1.1, large conductance Ca2+-activated K+ channel blocker (charybdotoxin), and by the KV, voltage-dependent K+ channel inhibitors (4-aminopyridine (4-AP) and tetraethylammonium chloride (TEA)). The antinociceptive effect produced by buprenorphine was blocked by the s.c. injection of 4-AP and TEA but not by L-NAME, ODQ, glibenclamide, glipizide, apamin, or charybdotoxin. The present results provide evidence for differences in peripheral mechanisms of action between these opioid drugs.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dor
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Transdução de Sinais
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Nociceptividade
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Analgésicos Opioides
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Antagonistas de Entorpecentes
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article