Lang E, Hord H A, Denson D
Division of Pain Medicine, Department of Anethesiology, Emory University School of Medicine,Atlanta, GA 30322,USA.
Pain. 1996 Nov;68(1):151-155. doi: 10.1016/S0304-3959(96)03223-X.
Venlafaxine hydrochloride (Effexor) is a structurally novel antidepressant that inhibits reuptake of 5-hydroxytryptamine and noradrenaline, but unlike the older antidepressants, has few side-effects. The objective of this study was to determine whether venlafaxine relieves thermal hyperalgesia in rats with neuropathic pain due to chronic constriction injury (CCI) of the sciatic nerve. Paw withdrawal latency (PWL) to heat was tested for each hind paw. A painful neuropathy was induced in 24 male Sprague-Dawley rats (Group 1) as described by Bennett and Xie. Rats randomly received either oral venlafaxine (22 mg/kg) or placebo via gavage feeding beginning the day after surgery. Postoperative PWL testing began 3 days after CCI (Time 0). A second group of 12 rats (Group 2) was used to confirm that venlafaxine reverses hyperalgesia in rats with a fully developed neuropathic lesion. These animals began to receive oral venlafaxine (22 mg/kg) starting on the third postoperative day, after the presence of thermal hyperalgesia was verified through PWL testing. Testing was continued for 5 days, during venlafaxine administration. A third group of 12 rats (Group 3) had activity measured before and after treatment with venlafaxine (22 mg/kg). Rats in the placebo group developed thermal hyperalgesia while those that received venlafaxine did not. Venlafaxine also appeared to have a mild non-specific analgesic effect that increased PWL in the sham limb. In Group 2, thermal hyperalgesia was present on day 3, but following treatment with venlafaxine, thermal hyperalgesia resolved. Activity measurements confirmed that venlafaxine was not sedating in this rat model.
盐酸文拉法辛(怡诺思)是一种结构新颖的抗抑郁药,它能抑制5-羟色胺和去甲肾上腺素的再摄取,但与较老的抗抑郁药不同,副作用较少。本研究的目的是确定文拉法辛是否能缓解坐骨神经慢性压迫损伤(CCI)所致神经性疼痛大鼠的热痛觉过敏。对每只后爪进行热刺激撤爪潜伏期(PWL)测试。按照Bennett和Xie的方法,在24只雄性Sprague-Dawley大鼠(第1组)中诱导出疼痛性神经病变。大鼠在手术后次日开始通过灌胃随机接受口服文拉法辛(22 mg/kg)或安慰剂。CCI术后3天(时间0)开始进行术后PWL测试。第二组12只大鼠(第2组)用于确认文拉法辛能逆转已完全形成神经性损伤大鼠的痛觉过敏。在通过PWL测试证实存在热痛觉过敏后,这些动物在术后第三天开始接受口服文拉法辛(22 mg/kg)。在文拉法辛给药期间持续测试5天。第三组12只大鼠(第3组)在接受文拉法辛(22 mg/kg)治疗前后测量活动情况。安慰剂组大鼠出现热痛觉过敏,而接受文拉法辛治疗的大鼠未出现。文拉法辛似乎还具有轻度非特异性镇痛作用,可增加假手术侧肢体的PWL。在第2组中,第3天出现热痛觉过敏,但在接受文拉法辛治疗后,热痛觉过敏消失。活动测量结果证实,在该大鼠模型中文拉法辛没有镇静作用。