Sex differences in the effects of amiloride on formalin test nociception in mice
Sex differences in the effects of amiloride on formalin test nociception in mice
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DOI：
10.1152/ajpregu.00902.2005
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发表时间：
2006-08-01
影响因子：
2.8
通讯作者：
Mogil, Jeffrey S.
中科院分区：
文献类型：
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作者：
Chanda, Mona Lisa;Mogil, Jeffrey S.
阿米洛利是一种非特异性的酸敏感离子通道（ASIC）的阻滞剂，最近已被牵连在机械和化学/炎症伤害性感受的调解。使用转基因模型的初步数据表明ASIC的作用存在性别差异。我们在此报告，阿米洛利（10-70 mg/kg ip）的全身给药在雌性而非雄性小鼠的福尔马林试验（5%; 20 μ l）中产生了对晚期/强直相伤害性行为的强有力的剂量依赖性阻断，完全消除了福尔马林试验反应中已知的性别差异。成人性腺切除术产生了一个“开关”的性别差异，阿米洛利疗效，与去势男性显示阿米洛利封锁和卵巢切除女性呈现阿米洛利敏感性降低。通过渗透性微型泵（分别为6 μ g/天或250 μ g/天），使用慢性苯甲酸雌激素或丙酸睾酮替代品可将性腺切除的小鼠转换回其完整状态。目前尚不清楚这种显著的性别差异是否是由于ASIC在疼痛处理中的性别特异性参与，但目前的数据代表了疼痛相关性别差异的首次证明之一，没有明显的阿片类药物参与。
Amiloride is a nonspecific blocker of acid-sensing ion channels (ASICs) that have been recently implicated in the mediation of mechanical and chemical/inflammatory nociception. Preliminary data using a transgenic model are suggestive of sex differences in the role of ASICs. We report here that systemic administration of amiloride (10-70 mg/kg ip) produces a robust, dose-dependent blockade of late/tonic phase nociceptive behavior on the mouse formalin test (5%; 20 mu l) in female but not male mice, completely abolishing the known sex difference in formalin test response. Adult gonadectomy produced a "switching" of sex differences in amiloride efficacy, with castrated males displaying an amiloride blockade and ovariectomized females rendered less sensitive to amiloride. Gonadectomized mice could be switched back to their intact status using chronic estrogen benzoate or testosterone propionate replacement via osmotic minipump (6 mu g/day or 250 mu g/day, respectively). It is unclear whether this striking sex difference is due to sex-specific involvement of ASICs in pain processing, but the present data represent one of the first demonstrations of pain-related sex differences with no obvious opioid involvement.