Involvement of spinal Met enkephalin in nicotine-induced antinociception in mice
Involvement of spinal Met enkephalin in nicotine-induced antinociception in mice
复制标题
DOI：
10.1016/j.brainres.2007.10.086
复制
发表时间：
2008-01-16
期刊：
影响因子：
2.9
通讯作者：
Kishioka, Shiroh
中科院分区：
文献类型：
--
作者：
Kiguchi, Norikazu;Maeda, Takehiko;Kishioka, Shiroh
尼古丁是中枢神经系统中的神经元刺激药物，通过烟碱乙酰胆碱受体发挥多种作用。如前所述，尼古丁通过激活内源性阿片神经元具有抗伤害感受作用。然而，尼古丁诱导的抗伤害感受的详细机制尚不确定。在本研究中，我们以小鼠脊髓为研究对象，探讨内源性阿片能神经元在尼古丁诱导的抗伤害感受中的作用。在夹尾试验中，皮下给予尼古丁（5 mg/kg）在尼古丁给药后0.5 h产生最大抗伤害感受;这被美加明（MEC，3 mg/kg，s.c.）或纳洛酮（NLX，lmg/kg，s.c.）局鞘内尼古丁（10 μ g）在2分钟时产生最大的抗伤害作用，MEC（3 mg/kg，s.c.）或NLX（1 mg/kg，s.c.）局脊髓前前脑啡肽原（ppENK）mRNA水平在尼古丁给药后2 h显著升高，但在尼古丁（5 mg/kg，s.c.）局MEC（3 mg/kg，s.c.）可抑制ppENK mRNA水平的增加。尼古丁（5 mg/kg，s.c.）未增加前强啡肽原和前阿黑皮素原的mRNA水平。在腰髓后角，尼古丁给药后0.5 h，甲硫氨酸-脑啡肽（Met-ENK）样IR显著降低，尼古丁（3 mg/kg，s.c.）局这些结果表明，尼古丁具有抗伤害效应，通过促进释放Met-ENK，而不是强啡肽和内啡肽，从激活的阿片样物质神经元在脊髓中。(c)2007 Elsevier B. V.保留所有权利。
Nicotine is neuronal stimulating drug in the central nervous system and elicits various effects through nicotinic acetylcholine receptors. As previously reported, nicotine has an antinociceptive effect through activation of endogenous opioid neurons. However, detailed mechanisms of nicotine-induced antinociception are uncertain. In this study, we focused on spinal cord and investigated the involvement of endogenous opioidergic neurons in nicotine-induced antinociception in mice. In the tail-pinch test, subcutaneously administered nicotine (5 mg/kg) produced maximal antinociception 0.5 h after nicotine administration; this was attenuated by mecamylamine (MEC, 3 mg/kg, s.c.) or naloxone (NLX, 1 mg/kg, s.c.) administration. Intrathecal nicotine (10 mu g) produced maximal antinociception at 2 min and this was also attenuated by MEC (3 mg/kg, s.c.) or NLX (1 mg/kg, s.c.) administration. The preproenkephalin (ppENK) mRNA level in spinal cord, but not dorsal root ganglion, was significantly increased 2 h following nicotine administration and recovered to control level 4 h after nicotine (5 mg/kg, s.c.) administration. This increase in ppENK mRNA level was inhibited by MEC (3 mg/kg, s.c.). The mRNA levels of preprodynorphin and preproopiomelanocortin were not increased by nicotine (5 mg/kg, s.c.). In the dorsal horn of the lumbar spinal cord, methionine-enkephalin (Met-ENK)-like IR was remarkably reduced at 0.5 h following nicotine administration and recovered to control levels by 2 h after nicotine (3 mg/kg, s.c.) administration. These results suggest that nicotine has an antinociceptive effect by promoting the release of Met-ENK, but not dynorphins and endorphins, from activated opioidergic neurons in spinal cord. (c) 2007 Elsevier B.V. All rights reserved.