Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia
Effects of selective inhibitors of neuronal nitric oxide synthase on carrageenan-induced mechanical and thermal hyperalgesia
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DOI：
10.1016/s0028-3908(97)00201-3
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发表时间：
1998-01-01
影响因子：
4.7
通讯作者：
Moore, PK
中科院分区：
文献类型：
--
作者：
Handy, RLC;Moore, PK
在大鼠足底注射角叉菜胶（150 μ l，2%w v（-1））后，测定了抑制一氧化氮合酶（NOS）对后爪痛觉过敏（用机械和热伤害性刺激评估）和水肿形成的影响。为此目的，使用NOS抑制剂，包括L-NG硝基精氨酸甲酯（L-NAME;同种型非选择性NOS抑制剂）、7-硝基吲唑（7-NI）和1-（2-三氟甲基苯基）咪唑（TRIM;两种神经元NOS的相对选择性抑制剂）。机械/热伤害性阈值和后爪重量记录之前和3小时后给予角叉菜胶。NOS抑制剂（5-25 mg/kg，i. p.）在角叉菜胶后2.5小时施用。L-NAME、7-NI和TRIM抑制角叉菜胶诱导的机械和热痛觉过敏。计算的艾德，值（μ mol kg（-1），i. p.）分别为63.4、96.2和92.7（机械）和42.2、53.9和62.1（热）。没有一种药物影响非注射后爪或角叉菜胶诱导的后爪增重中的疼痛感知。因此，7-NI和TRIM，在以前报道的剂量不影响心血管血流动力学，抑制大鼠痛觉过敏，无论采用的有害刺激的类型。因此，神经元NOS的选择性抑制剂可能被证明可用于治疗人类的长期疼痛。（C）1998 Elsevier Science Ltd.保留所有权利。
The effect of inhibition of nitric oxide synthase (NOS) on hindpaw hyperalgesia (assessed using mechanical and thermal noxious stimuli) and oedema formation following intraplantar injection of carrageenan (150 mu l, 2% w v(-1)) in the rat was determined. For this purpose, NOS inhibitors including L-NG nitro-arginine methyl ester (L-NAME; isoform non-selective NOS inhibitor), 7-nitroindazole (7-NI) and 1-(2-trifluoromethylphenyl) imidazole (TRIM; both relatively selective inhibitors of neuronal NOS) were used. Mechanical/thermal nociceptive threshold values and hindpaw weight were recorded prior to and 3 h after administration of carrageenan. NOS inhibitors (5-25 mg kg(-1), i.p.) were administered 2.5 h after carrageenan. L-NAME, 7-NI and TRIM inhibited carrageenan-induced mechanical and thermal hyperalgesia. Calculated ED,, values (mu mol kg(-1), i.p.) were 63.4, 96.2 and 92.7 (mechanical) and 42.2, 53.9 and 62.1 (thermal), respectively. None of the drugs affected pain perception in the non-injected hindpaw or carrageenan-induced hindpaw weight gain. Thus, 7-NI and TRIM, at doses previously reported not to influence cardiovascular haemodynamics, inhibit hyperalgesia in the rat regardless of the type of noxious stimulus employed. Accordingly, selective inhibitors of neuronal NOS may prove useful for the treatment of prolonged pain in man. (C) 1998 Elsevier Science Ltd. All rights reserved.