期刊
NEUROSCIENCE LETTERS
卷 467, 期 1, 页码 48-52出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2009.10.016
关键词
Sex-differences; Clonidine; Pain; Head withdrawal test; NMDA
资金
- NIH [8SC1 NS063951, U54 NS041071, RR03032]
Activation of the alpha(2)-adrenoceptor has been shown to produce antinociception. We have previously shown that the antinociceptive effect of clonidine, an alpha(2)-adrenoceptor agonist, is sex-specific and is abolished exogenous estrogen in ovariectomized rats or high level of endogenous estrogen in proestrous females Here, we investigated whether testosterone mediates the antinociceptive effect of clonidine in the trigeminal region of the male rat. Clonidine (7 mu g/5 mu l) was injected intracisternally through a PE-10 cannulation implanted dorsal to the trigeminal region in orchidectomized (GDX) male Sprague-Dawley rats. In separate groups, testosterone propionate (250 mu g/100 mu l: GDX+T) or beta-estradiol benzoate (100 mu g/100 mu l; GDX+E) were injected subcutaneously 24 and 48 h respectively prior to the N-methyl-D-aspartic acid (NMDA)-or heat-evoked nociceptive test. NMDA-induced number of scratches or duration of scratching behavior did not change significantly in control groups with or without hormonal replacement. Clonidine significantly reduced both measures only in the GDX+T group but not in GDX or GDX+E group. Clonidine also significantly increased head withdrawal latency (HWL) in the GDX+Tgroup, but not in GDX or GDX+E group. The antinociceptive effect of clonidine was reversed by yohimbine, an alpha(2)-adrenoceptor antagonist, in GDX+T group. We conclude that testosterone is required for the expression of antinociception produced by selective activation of the alpha(2)-adrenoceptor in the trigeminal region of the male rat. These findings further our understanding of sex-related differences in the modulation of nociception and may provide insight into development and administration of analgesic agents in young vs. aging men. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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