Treatment of a chronic allodynia-like response in spinally injured rats: Effects of systemically administered nitric oxide synthase inhibitors

被引:68
作者
Hao, JX [1 ]
Xu, XJ [1 ]
机构
[1] HUDDINGE UNIV HOSP, KAROLINSKA INST, DEPT LAB MED SCI & TECHNOL, CLIN NEUROPHYSIOL SECT, S-14186 HUDDINGE, SWEDEN
关键词
allodynia; analgesia; blood pressure; L-NAME; nitric oxide; pain; rat; spinal cord injury; 7-nitro indazole;
D O I
10.1016/0304-3959(96)03039-4
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
We have previously reported that we have observed chronic pain-like response to light mechanical stimuli (allodynia) in rats after severe spinal cord ischemia, which resembles some painful conditions in chronic spinally injured patients and is not relieved by a number of conventional analgesics used for treating chronic neuropathic pain. In the present study, we tested the effects of the non-selective nitric oxide synthase (NOS) inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) and the selective neuronal NOS inhibitor 7-nitro indazole (7-NI) and 6-nitro indazole (6-NI) on the chronic allodynia-like behavior. Systemic L-NAME dose-dependently relieved mechanical allodynia-like response in a stereo-specific and L-arginine-reversible manner without causing sedation or motor deficits. However, L-NAME significantly elevated systemic blood pressure. Systemic 7-NI relieved chronic allodynia in a L-arginine reversible manner, did not increase blood pressure or induce sedation, but caused motor deficits at a high dose, which was not reversed by L-arginine. Systemic 6-NI also relieved the chronic allodynia, which was however associated with severe sedation. In order to exclude the possibility that the effect of L-NAME on blood pressure was involved in the analgesic effect observed, the effect of systemically applied adrenaline was examined. Adrenaline increased the systemic blood pressure to a similar extent as L-NAME, but did not relieve allodynia. It is suggested that blockade of NOS by L-NAME relieved the chronic allodynia-like behavior in spinally injured rats. This effect was likely to be mediated by a blockade of neuronal isoforms of NOS, as 7-NI relieved the allodynia in a L-arginine-reversible manner. Consequently, generation of NO by neuronal NOS may be critically involved in the maintenance of this abnormal pain-related sensation. The possibility of using NOS inhibitors as potential novel analgesics is discussed.
引用
收藏
页码:313 / 319
页数:7
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