Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist

被引:78
作者
Cahill, CM
Coderre, TJ [1 ]
机构
[1] Clin Res Inst Montreal, Pain Mech Lab, Montreal, PQ, Canada
[2] McGill Univ, Dept Anesthesia, Anesthesia Res Unit, Montreal, PQ H3G 1Y6, Canada
[3] McGill Univ, Dept Psychol, Montreal, PQ, Canada
基金
加拿大健康研究院; 英国医学研究理事会;
关键词
substance P; neuropath; allodynia; nociception; analgesia; sciatic nerve constriction;
D O I
10.1016/S0304-3959(01)00410-9
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
Although many studies have demonstrated a role for substance Pin pain, there have been conflicting reports implicating the involvement of substance P in neuropathic pain models. In this study, the non-peptide neurokinin-1 (NK-1) receptor antagonist. L-732,138 was chronically administered by intrathecal (i.t.) injection to rats with mono-neuropathy produced by sciatic nerve constriction. Rats exhibited tactile ministered i.t. prior to and for 3 consecutive days allodynia and cold hyperalgesia over a 16-day testing period. L-732,138 (5-200 nmol) administered i.t. prior to and for 3 consecutive days post-surgery attenuated the mechanical allodynia and cold hyperalgesia on days 4 and 8 post-surgery. The effects of i.t. L-732,138 were also determined in rats with established nerve injury-induced neuropathy. The NK-1 receptor antagonist was injected for 4 consecutive days starting on day 8 post-sciatic nerve injury. Administration of L-731 138 (5-200 nmol) i.t. produced both anti-allodynic and anti-hyperalgesic effects on day 12, but the effect was not permanent, as nociceptive thresholds were similar to controls by day 16. These results demonstrate that substance P is involved both in the induction and the maintenance of neuropathic pain and provides justification for the development and administration of substance P antagonists for the management of clinical neuropathic pain. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:277 / 285
页数:9
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