A possible role of sympathetic nervous system on expression of adrenergic receptors in the dorsal root ganglion neuron in rats

交感神经系统对大鼠背根神经节肾上腺素能受体表达的可能作用

• 批准号: 07680826
• 负责人: NISHIYAMA Keiji
• 金额: $ 1.41万
• 依托单位: Fukushima Medical University, School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680826/
• 关键词: α2-adrenergic receptor; dorsal root ganglion; sympathetic nerve; nerve injury; hyperalgesia; noradrenalin; capsaicin; α2-アドレナリン受容体; ニューロトロフィン受容体; 後根神経節ニューロン; 脊髄後角; 痛覚上行路

Chronic pain like causalgia, phantom pain, and reflex sympathetic dystrophy, is caused by peripheral nerve injury. Pain mechanisms of these syndromes were still not clear, in spite of many hypotheses. Sato and Perl (Science, 1991) reported that peripheral nerve injury induces an adrenergic excitability in normal C-fiber nociceptors that is mediated through an adrenergic receptor(AR) with α2 pharmacological characteristics. The present research examined the effects of injury to limb nerves (sciatic or tibial) or the lumbar sympathetic trunk(SYX) on changes of expression of α2-AR in the dorsal root ganglion(DRG), changes of responsiveness to noradrenalin treatment, and determination of possible expression of α2-AR subtypes. These projects showed the results below. (1) The DRG neurons, mainly small size cells increased the binding of clonidine, α2-AR agonist, by nerve injuries and SYX. (2) Following noradrenaline injection into the plantar subcutis suffered SYX, Fos protein expression as a marker of activated neurons augmented in the spinal dorsal horn, especially laminae I and II. This phenomenon may be induced by increased nociceptive inputs from DRG neurons activated by SYX . A stimulant of the C-fiber,capsaicin also showed the enhanced responsiveness by SYX. (3) The increased expression of α2-AR subtypes was showed in α2C subtype, using in situ hybridization with oligoprobes coding mRNAs of α2-AR subtypes, α2A and α2C. The expression of trk receptors also showed increase of trkC only by SYX. These results suggested that peripheral nerve injury including the sympathetic nerve may cause hyperalgesia due to the increased expression of the α2-AR in the DRG neuron.

慢性疼痛如头痛、幻痛和反射性交感神经营养不良是由周围神经损伤引起的。这些综合征的疼痛机制仍不清楚，尽管有许多假说。Sato和Perl（Science，1991）报道，外周神经损伤诱导正常C纤维伤害感受器中的肾上腺素能兴奋性，其通过具有α2药理学特征的肾上腺素能受体（AR）介导。本研究观察了肢体神经（坐骨神经、胫神经）或腰交感干（SYX）损伤后背根神经节（DRG）α2-AR表达的变化，对去甲肾上腺素治疗反应性的变化，以及α2-AR亚型的可能表达。这些项目取得了以下成果。(1)DRG神经元以小细胞为主，神经损伤后与SYX结合的α2-AR激动剂可乐定增加。(2)在去甲肾上腺素注射到足底皮下组织遭受SYX后，Fos蛋白表达作为激活的神经元的标记在脊髓背角，特别是板层I和II增加。这种现象可能是由SYX激活的DRG神经元增加的伤害性输入引起的。辣椒素是一种C-纤维的兴奋剂，也显示出对SYX的增强反应。(3)用编码α2-AR亚型、α2A和α2C mRNA的寡核苷酸探针进行原位杂交，发现α2-AR亚型在α2C亚型中表达增加。trk受体的表达也显示trkC仅由SYX增加。结果提示，周围神经损伤（包括交感神经损伤）可能与DRG神经元α2-AR表达增加有关。

项目成果

TONOSAKI,Y et al: "α-MSH modulates Fos expression in paraventricular nucleus of the hypothalamus induced by interleukin-1 β in rats" Proceedinga of the XIII^<th> Intenational Congress of Comparative Endocrinology. 1027-1032 (1997)

TONOSAKI，Y 等人：“α-MSH 调节大鼠下丘脑室旁核中由白细胞介素 1 β 诱导的 Fos 表达”第十三届国际比较内分泌学大会论文集 1027-1032（1997 年）。

K. Nishiyama, Y. Tonosaki, T. Honda, N. Ozaki, Y. Sigiura: "An increase of α2-adrenergic receptors in the DRG neurons by sympathectomy promotes a Fos expression in the dorsal horn"Neuroscience Res.. 20. S208 (1996)

K. Nishiyama、Y. Tonosaki、T. Honda、N. Ozaki、Y. Sigiura：“通过交感神经切除术增加 DRG 神经元中的 α2-肾上腺素受体可促进背角中的 Fos 表达”神经科学研究 20. S208 (1996)

TONOSAKI,Y et al: "MSH modulate Fos expression in paraventricular nucleus and hyperalgesia induced by intracerebroventricular administration of interleukin-1β" Neuroscience Research Suppl.20. S108- (1996)

TONOSAKI,Y 等人：“MSH 调节室旁核中 Fos 的表达以及脑室内注射白细胞介素 1β 引起的痛觉过敏”神经科学研究增刊 S108-(1996)。

K. Nishiyama, Y. Tonosaki, T. Honda, N. Ozaki, Y. Sigiura: "An increase of α2-adrenergic receptors in the DRG neurons by sympathectomy promotes a Fos expression in the dorsal horn"Acta Anat. Nippon.. 71. 411 (1996)

K. Nishiyama、Y. Tonosaki、T. Honda、N. Ozaki、Y. Sigiura：“通过交感神经切除术增加 DRG 神经元中的 α2 肾上腺素受体可促进背角中的 Fos 表达”Acta Anat.. 71 .411 (1996)

NISHIYAMA,K et al: "An increase of α2-adrenergic receptors in the DRGs by sympathectomy promotes a Fos expression in the dorsal horn" Neuroscience Research Suppl.20. S208- (1996)

NISHIYAMA,K 等人：“通过交感神经切除术增加 DRG 中的 α2-肾上腺素受体可促进背角中的 Fos 表达”Neuroscience Research Suppl.20-(1996)。