title: Role of ATP-sensitive K+ channels in the antinociception induced by non-steroidal anti-inflammatory drugs in streptozotocin-diabetic and non-diabetic rats.
abstract: There is evidence that systemic sulfonylureas block diclofenac-induced antinociception in normal rat, suggesting that diclofenac activates ATP-sensitive K(+) channels. However, there is no evidence for the systemic interaction between different non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonylureas in streptozotocin (STZ)-diabetic rats. Therefore, this work was undertaken to determine whether two sulfonylureas, glibenclamide and glipizide, have any effect on the systemic antinociception that is induced by diclofenac (30 mg/kg), lumiracoxib (56 mg/kg), meloxicam (30 mg/kg), metamizol (56 mg/kg) and indomethacin (30 mg/kg) using the non-diabetic and STZ-diabetic rat formalin test. Systemic injections of NSAIDs produced dose-dependent antinociception during the second phase of the test in both non-diabetic and STZ-diabetic rats. Systemic pretreatment with glibenclamide (10 mg/kg) and glipizide (10 mg/kg) blocked diclofenac-induced systemic antinociception in the second phase of the test (P<0.05) in both non-diabetic and STZ-diabetic rats. In contrast, pretreatment with glibenclamide or glipizide did not block lumiracoxib-, meloxicam-, metamizol-, and indomethacin-induced systemic antinociception (P>0.05) in both groups. Results showed that systemic NSAIDs are able to produce antinociception in STZ-diabetic rats. Likewise, data suggest that diclofenac, but not other NSAIDs, activated K(+) channels to induce its systemic antinociceptive effect in the non-diabetic and STZ-diabetic rat formalin test.
authors.affiliation: Área Académica de Medicina del Instituto de Ciencias de lSalud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo, Mexico. mario_i_ortiz@hotmail.com
authors.forename: Mario I
authors.initials: MI
authors.lastname: Ortiz
authors.forename: Gilberto
authors.initials: G
authors.lastname: Castañeda-Hernández
authors.forename: Jeannett A
authors.initials: JA
authors.lastname: Izquierdo-Vega
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Gutiérrez
authors.forename: Héctor A
authors.initials: HA
authors.lastname: Ponce-Monter
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D054086:KATP Channels / Q000819:agonists* / Q000502:physiology*; D008297:Male; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D054086:KATP Channels