TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw
TRPA1, NMDA receptors and nitric oxide mediate mechanical hyperalgesia induced by local injection of magnesium sulfate into the rat hind paw
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DOI：
10.1016/j.physbeh.2014.11.042
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发表时间：
2015-02-01
影响因子：
2.9
通讯作者：
Prostran, Milica S.
中科院分区：
文献类型：
--
作者：
Srebro, Dragana P.;Vuckovic, Sonja M.;Prostran, Milica S.
先前的研究表明，虽然镁是n -甲基- d -天冬氨酸受体谷氨酸亚型的拮抗剂，具有镇痛特性，但它可以引起啮齿动物的扭动。本研究的目的是确定局部（足底）给药硫酸镁（MS）对机械刺激下足爪戒断阈值（PWT）的影响和作用机制。采用电子von Frey法评价雄性Wistar大鼠的PWT。试验药物要么与MS同时在跖内（i.pl）给药，要么给药到对侧足部，以排除全身影响。剂量为0.5、1.5、3和62 mg/paw （i.pl.）的MS诱导了具有统计学意义的（与0.9% NaCl相比）和剂量依赖性的机械痛觉过敏。只有等渗MS （250 mmol/l或6.2%或62 mg/只爪）能引起持续至少6小时的机械性痛觉过敏。共注射樟脑、非选择性TRPA1拮抗剂（0.3、1和2.5 μ g/爪）、NMDA受体拮抗剂MK-801（0.001、0.025和0.1 μ g/爪）、非选择性一氧化氮（NO）合成酶抑制剂L-NAME（20、50和100 μ g/爪）、选择性神经元NOS抑制剂ARL 17477（5.7和17 μ g/爪）、选择性诱导型NOS抑制剂SMT（1和2.78 μ g/爪）和亚甲基蓝，均能以剂量依赖性方式减轻等张ms诱导的机械性痛觉过敏。鸟苷酸环化酶抑制剂（5、20和125 μ g/爪）。对侧后爪注射药物无明显作用。这些结果表明，一个i.pl。注射MS通过激活外周TRPA1和NMDA受体以及外周NO的产生产生局部外周机械性痛觉过敏。(c) 2014 Elsevier Inc.版权所有。
Previous studies have shown that while magnesium, an antagonist of the glutamate subtype of N-methyl-D-aspartate receptors, possesses analgesic properties, it can induce writhing in rodents. The aim of this study was to determine the effect and mechanism of action of local (intraplantar) administration of magnesium sulfate (MS) on the paw withdrawal threshold (PWT) to mechanical stimuli. The PWT was evaluated by the electronic von Frey test in male Wistar rats. Tested drugs were either co-administered intraplantarly (i.pl.) with MS or given into the contralateral paw to exclude systemic effects. MS at doses of 0.5, 1.5, 3 and 62 mg/paw (i.pl.) induced a statistically significant (as compared to 0.9% NaCl) and dose-dependent mechanical hyperalgesia. Only isotonic MS (250 mmol/l or 6.2% or 62 mg/paw) induced mechanical hyperalgesia that lasted at least six hours. Isotonic MS-induced mechanical hyperalgesia was reduced in a dose-dependent manner by co-injection of camphor, a non-selective TRPA1 antagonist (0.3, 1 and 2.5 mu g/paw), MK-801, a NMDA receptor antagonist (0.001, 0.025 and 0.1 mu g/paw), L-NAME, a non-selective nitric oxide (NO) synthase inhibitor (20, 50 and 100 mu g/paw), ARL 17477, a selective neuronal NOS inhibitor (5.7 and 17 mu g/paw), SMT, a selective inducible NOS inhibitor (1 and 2.78 mu g/paw), and methylene blue, a guanylate cyclase inhibitor (5, 20 and 125 mu g/paw). Drugs injected into the contralateral hind paw did not produce significant effects. These results suggest that an i.pl. injection of MS produces local peripheral mechanical hyperalgesia via activation of peripheral TRPA1 and NMDA receptors and peripheral production of NO. (c) 2014 Elsevier Inc. All rights reserved.