Renin Angiotensin Sytem irt Patients with Neuropathic Pain

肾素血管紧张素系统治疗神经性疼痛患者

• 批准号: 11671492
• 负责人: KIMURA Tomomasa
• 金额: $ 2.5万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671492/
• 关键词: Neuropathic Pain; CRPS; Renin-Angiotensin; Angiotensinogen; ACE; Chronic Constriction Model; SHR; Antisense-QDN; ニューロパシックペイン; アンジオテンシノーゲン; Bennefモデル

The aim of this study was to explore whether renin-angiotensin axix associates neuropathic pain. ACE gene polymorphism (DD and II homozygotes, and ID heterozygotes) associates the genetic risk factor for neuropathic pain. The distribution of the DD, ID and II genotypes in the study group is 33%, 33% and 33%, respectively. ACE activity was significantly higher in subjects with the ACE DD genotype than subjects with the ID and H genotypes. No significant difference in heart rate and blood pressure variabilities, plasma renin activity, angiotensin I and II was detected among the ACE genotypes. The frequency of the ACE DD genotype in the present population (33%) was higher than those previously described in other normal populations of the same race (20%).3 In addition, the frequency of the ACE DD genotype in CRPS type I was higher than those in CRPS type IIIt is possible that the DD genotype favors the development of neuropathic pain as well as cardiovascular disease, perhaps through the p … More resence of higher ACE concentrations. Elevated ACE activity in these subjects may result in increased angiotensin n levels in the effector site, and this might be a mechanism underlying the association between the ACE deletion polymorphism and the increased genetic risk for susceptibility to neuropathic pain. Typing for ACE I/D gene poly-morphism, thus, might be a useful predictor of neuropathic pain.Aim of Investigation : Increased nociceptive thresholds have been reported in hypertensive rats and humans. Spontaneous hypertensive rats (SHR) have been known to have increased sympathetic tones which might alter the peripheral mononeuropathy. To test this hypothesis, we measured peripheral nerve injury-induced heat allodynia in SHR.Methods : Chronic constrictive injury (CCI) was produced by loosely ligation of the unilateral sciatic nerve in normotensive Sprague-Dawely (SD) rat and SHR. The magnitude of the hyperesthesia was evaluated with the difference score (DS) which was the result of subtracting the latency of the withdrawal reflex on the control (sham-operated) side from the latency on the nerve injured side to the radiant heat stimulation. Systolic blood pressure (SBP) was oscillometrically measured. Data were expressed as meanアSEM, and analyzed by ANOVA. P<0.05 was considered significant.Results : SD rats undergoing CCI showed decrease in DS from 0.85【minus-plus】0.39 before CCI to 1.67【minus-plus】1.12, -2.51【minus-plus】2.07 and -0.63【minus-plus】0.83, 4, 7 and 14days after CCI, respectively. On the contrary, DS hi SHR unchanged throughout the measurement, from -1.58【minus-plus】0.87 before CCI to 0.2【minus-plus】0.49, -0.85【minus-plus】0.83 and -1.95【minus-plus】1.02, 4, 7 and 14days after CCI, respectively.SBP before CCI were 126【minus-plus】8 (SD) and 177【minus-plus】6 (SHR).Conclusions : SHR have been reported to have decreased sensitivity to pain, but as yet a mechanism has not been identified. CCI model hi SHR caused a reduction hi thermal hyperalgesia, indicating that a genetic predisposition to hypertension may attenuate the mononeuropathic thermal hyperlgesia Less

本研究的目的是探讨肾素-血管紧张素轴是否与神经性疼痛相关。 ACE 基因多态性（DD 和 II 纯合子，以及 ID 杂合子）与神经性疼痛的遗传风险因素相关。研究组中DD、ID和II基因型的分布分别为33%、33%和33%。具有 ACE DD 基因型的受试者的 ACE 活性显着高于具有 ID 和 H 基因型的受试者。 ACE 基因型之间的心率和血压变异性、血浆肾素活性、血管紧张素 I 和 II 没有检测到显着差异。当前人群中 ACE DD 基因型的频率 (33%) 高于先前在同一种族的其他正常人群中描述的频率 (20%)。3 此外，I 型 CRPS 中 ACE DD 基因型的频率高于 III 型 CRPS 中的频率，这可能是因为 DD 基因型有利于神经性疼痛和心血管疾病的发展，可能是通过较高 ACE 浓度的存在。这些受试者中 ACE 活性升高可能导致效应位点血管紧张素 n 水平升高，这可能是 ACE 缺失多态性与神经性疼痛易感性遗传风险增加之间关联的潜在机制。因此，ACE I/D 基因多态性的分型可能是神经性疼痛的有用预测因子。 研究目的：据报道，高血压大鼠和人类的伤害性阈值增加。已知自发性高血压大鼠（SHR）的交感神经张力增加，这可能会改变周围单神经病。为了检验这一假设，我们测量了 SHR 中周围神经损伤引起的热异常性疼痛。方法：通过松散结扎正常血压 Sprague-Dawely (SD) 大鼠和 SHR 的单侧坐骨神经来产生慢性缩窄性损伤 (CCI)。感觉过敏的程度用差值(DS)来评价，差值是从神经损伤侧的潜伏期减去对照(假手术)侧的撤回反射的潜伏期到辐射热刺激的结果。通过示波法测量收缩压（SBP）。数据表示为平均值SEM，并通过方差分析进行分析。 P<0.05被认为是显着的。结果：接受CCI的SD大鼠的DS从CCI前的0.85【负加】0.39分别下降到CCI后0.83、4、7和14天的1.67【负加】1.12、-2.51【负加】2.07和-0.63【负加】。相反，DS hi SHR 在整个测量过程中保持不变，从 CCI 前的 -1.58【负+】0.87 分别变为 CCI 后 1.02、4、7 和 14 天的 0.2【负+】0.49、-0.85【负+】0.83 和 -1.95【负+】。 126【负加】8 (SD) 和 177【负加】6 (SHR)。结论：据报道，SHR 对疼痛的敏感性降低，但尚未确定其机制。 CCI 模型 hi SHR 导致 hi 热痛觉过敏减少，表明高血压的遗传倾向可能会减弱单神经性热痛觉过敏 Less

项目成果

細田蓮子: "セロトニン受容体(5-HTR_<2A>)遺伝子多型T102Cと慢性疼痛疾患の関連にるいて."平成11年度セロトニン(5-HT_2)研究会報告. 32-33 (2000)

Renko Hosoda：“血清素受体 (5-HTR_<2A>) 基因多态性 T102C 与慢性疼痛疾病之间的关系。”1999 年血清素 (5-HT_2) 研究小组报告。

Hosoda, R: "Association between chronic pain and T1O2C polymorphism of the 5-HTR_<2A> gene"Proceedings of World Wide Pain Conference. 7. 43-47 (2000)

Hosoda，R：“慢性疼痛与5-HTR_<2A>基因的T1O2C多态性之间的关联”世界疼痛会议论文集。

Tomomasa Kimura: "Angiotensin-converting enzyme gene polymorphism in patients with neuropathic pain."Proceedings of the 9th World Congress on Pain. 16. 471-476 (2000)

Tomomasa Kimura：“神经性疼痛患者的血管紧张素转换酶基因多态性。”第九届世界疼痛大会论文集。

Renko Hosoda: "Association Between Chronic Pain and T102C polymorphism of the 5-HTR_<2A> Gene"Proceedings of Worldwide pain Conference. 43-47 (2000)

Renko Hosoda：“慢性疼痛与5-HTR_<2A>基因的T102C多态性之间的关联”世界疼痛会议论文集。

木村智政: "CRPS患者におけるアンジオテンシノーゲン遺伝子多型"J of Anesthesia. 14(suppl). 73-73 (2000)

Tomomasa Kimura：“CRPS 患者的血管紧张素原基因多态性”J of Anesthesia 14(suppl)。