Rode Frederik, Broløs Tine, Blackburn-Munro Gordon, Bjerrum Ole J
Department of Pharmacology, Danish University of Pharmaceutical Sciences, Jagtvej 120, Copenhagen, Denmark.
Psychopharmacology (Berl). 2006 Aug;187(3):364-75. doi: 10.1007/s00213-006-0430-3. Epub 2006 Jun 17.
Neuropathic pain is associated with a number of disease states of diverse aetiology that can share common pathophysiological mechanisms. Antiepileptic drugs modulate ion channel function and antidepressants increase extracellular monoamine levels, and both drug classes variously attenuate signs and symptoms of neuropathic pain. Thus, coadministration of the antiepileptic gabapentin and the antidepressant venlafaxine may provide superior pain relief to administration of either drug alone.
To systematically establish the pain relieving efficacies of venlafaxine and gabapentin alone and in combination.
Gabapentin (50 and 100 mg/kg, s.c.) and venlafaxine (10, 25, 50 mg/kg, s.c.) were tested alone or in combination in the rat spared nerve injury (SNI) model of neuropathic pain and the rat formalin test of persistent pain. Diuresis was measured in a separate experiment after administration of venlafaxine.
Hindpaw mechanical allodynia was dose-dependently reversed by gabapentin (50 and 100 mg/kg, s.c.), whereas venlafaxine was ineffective (10 and 50 mg/kg, s.c.). Both gabapentin and venlafaxine also attenuated hindpaw mechanical hyperalgesia. Surprisingly, coadministration of venlafaxine (50 mg/kg) significantly lowered the antiallodynic effect of both doses of gabapentin by up to 60% in spared-nerve-injury rats and a negative antinociceptive interaction between gabapentin and venlafaxine was also observed in the rat formalin test. We demonstrated that venlafaxine administration was associated with a dose-dependent increase in urine output over the time course of the nociceptive experiments.
Venlafaxine compromises the antiallodynic effects of coadministered gabapentin most probably as consequence-increased diuresis.
神经性疼痛与多种病因各异的疾病状态相关，这些疾病状态可能具有共同的病理生理机制。抗癫痫药物可调节离子通道功能，而抗抑郁药物可提高细胞外单胺水平，这两类药物均可不同程度地减轻神经性疼痛的体征和症状。因此，抗癫痫药物加巴喷丁与抗抑郁药物文拉法辛联合使用可能比单独使用任一药物能更有效地缓解疼痛。
系统地确定文拉法辛和加巴喷丁单独使用及联合使用时的止痛效果。
在神经性疼痛的大鼠 spared 神经损伤（SNI）模型和持续性疼痛的大鼠福尔马林试验中，单独或联合测试加巴喷丁（50 和 100mg/kg，皮下注射）和文拉法辛（10、25、50mg/kg，皮下注射）。在给予文拉法辛后的另一项实验中测量利尿情况。
加巴喷丁（50 和 100mg/kg，皮下注射）可剂量依赖性地逆转后爪机械性异常性疼痛，而文拉法辛（10 和 50mg/kg，皮下注射）无效。加巴喷丁和文拉法辛也均可减轻后爪机械性痛觉过敏。令人惊讶的是，在 spared 神经损伤大鼠中，联合使用文拉法辛（50mg/kg）可使两种剂量加巴喷丁的抗异常性疼痛作用显著降低多达 60%，并且在大鼠福尔马林试验中也观察到加巴喷丁与文拉法辛之间存在负性抗伤害感受相互作用。我们证明，在伤害感受实验过程中，给予文拉法辛与尿量呈剂量依赖性增加有关。
文拉法辛可能由于利尿增加而损害联合使用的加巴喷丁的抗异常性疼痛作用。
