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The role of α7-nicotinic acetylcholine receptor in a rat model of chronic nicotine-induced mechanical hypersensitivity
Neuroscience Letters ( IF 2.5 ) Pub Date : 2020-12-19 , DOI: 10.1016/j.neulet.2020.135566
Yanping Zhang , Alec Sevilla , Robert Weller , Shuju Wang , Melvin C. Gitlin , Keith A. Candiotti

Smokers have a higher incidence of chronic pain than non-smokers, but the neural mechanism is not yet fully understood. Nicotine is the main component of tobacco and acts as an agonist for nicotinic cholinergic receptors (nAChRs) in the nervous system.

This study was approved by the IACUC of UM. The effects of chronic nicotine administration on mechanical sensitivity were studied using a rat model. The changes in the expression levels of the α7 isoform of nAChR (α7-nAChR), inflammatory cytokines TNFα and COX-2, as well as the density of neuro-immune cells (astrocytes and microglia) were measured concurrently.

The results indicate that long-term nicotine administration induces hypersensitivity to mechanical stimuli, as demonstrated by a significant reduction in the pain perception threshold. In response to nicotine, the expression levels of α7-nAChR increased in the periaqueductal gray matter (PAG) and decreased in the spinal cord. Acute administration of the selective α7-nAChR agonist CDP-Choline reversed this hypersensitivity. Chronic nicotine administration led to an increase of microglial cells in the dorsal horn of the spinal cord and increased expression levels of the cytokines TNFα and COX-2.

This study suggests that decreased α7-nAChR expression in the spinal cord, as a result of long-term exposure to nicotine, may be causatively linked to chronic pain. Simultaneously, the increase of neuro-immune factors in the spinal cord is also a potential factor leading to chronic pain.



中文翻译:

α7-烟碱乙酰胆碱受体在慢性尼古丁诱发的机械性超敏反应大鼠模型中的作用

吸烟者比非吸烟者有更高的慢性疼痛发生率,但神经机制尚未完全明了。尼古丁是烟草的主要成分,并充当神经系统中烟碱胆碱能受体(nAChRs)的激动剂。

这项研究得到了UM的IACUC的批准。使用大鼠模型研究了慢性尼古丁给药对机械敏感性的影响。同时测量nAChR的α7亚型(α7-nAChR),炎性细胞因子TNFα和COX-2的表达水平以及神经免疫细胞(星形胶质细胞和小胶质细胞)的密度的变化。

结果表明,长期服用尼古丁会引起对机械刺激的超敏反应,这可通过明显降低疼痛感阈值来证明。响应尼古丁,α7-nAChR的表达水平在导水管周围灰质(PAG)中升高,而在脊髓中降低。选择性α7-nAChR激动剂CDP-胆碱的急性给药逆转了这种超敏反应。长期服用尼古丁可导致脊髓背角小胶质细胞增加,并增加细胞因子TNFα和COX-2的表达水平。

这项研究表明,长期暴露于尼古丁导致脊髓中α7-nAChR表达降低,可能与慢性疼痛有关。同时,脊髓中神经免疫因子的增加也是导致慢性疼痛的潜在因素。

更新日期:2020-12-24
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