Pharmacological interaction between gabapentin and glibenclamide in the formalin test in the diabetic rat.

Mario I Ortiz, Héctor A Ponce-Monter, Eduardo Fernández-Martínez, Arturo Macías, Eduardo Rangel-Flores, Jeannett A Izquierdo-Vega, Manuel Sánchez-Gutiérrez
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Abstract

There is evidence that local peripheral administration of gabapentin produces antinociception through the activation of the ATP-sensitive K+-channel. However, this interaction has not been evaluated systemically, nor in diabetic rat. This work was undertaken to determine whether glibenclamide has any effect on the systemic antinociception induced by gabapentin. Inflammatory pain was induced by injection of formalin in diabetic rats. Reduction of flinching behavior was considered as antinociception. Systemic administration of gabapentin (10-56 mg/kg, i.p.) produced a dose-dependent antinociception in both phases of the formalin test. Also, glibenclamide (1-10 mg/kg, s.c.) blocked the gabapentin-induced antinociception. Given alone glibenclamide did not significantly modify formalin-induced nociception in diabetic rats. Our data suggest that gabapentin is able to reduce formalin-induced nociception in streptozotocin-injected rats. In addition, these data are consistent with gabapentin-mediated activation of ATP-sensitive-K+ channels to produce systemic antinociception in the formalin test in diabetic rats.

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糖尿病大鼠福尔马林试验中加巴喷丁与格列本脲的药理相互作用。
有证据表明,局部外周给药加巴喷丁通过激活atp敏感的K+通道产生抗痛觉。然而,这种相互作用还没有被系统地评估,也没有在糖尿病大鼠中评估。这项工作是为了确定格列本脲是否对加巴喷丁诱导的全身抗伤性有任何影响。采用注射福尔马林诱导糖尿病大鼠炎症性疼痛。减少退缩行为被认为是抗感觉。全身给药加巴喷丁(10-56 mg/kg, i.p)在福尔马林试验的两个阶段都产生剂量依赖性的抗痛觉作用。格列本脲(1 ~ 10mg /kg, s.c)阻断加巴喷丁诱导的抗痛觉作用。单给格列苯脲对糖尿病大鼠福尔马林引起的伤害感觉无明显改善作用。我们的数据表明,加巴喷丁能够减少福尔马林诱导的链脲佐菌素注射大鼠的伤害感受。此外,在糖尿病大鼠的福尔马林试验中,这些数据与加巴喷丁介导的atp敏感- k +通道激活产生全身抗伤感受一致。
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