B族维生素在治疗慢性疼痛中的地位及作用机制讨论

2005-09-06 00:00 来源:麻醉疼痛专业讨论版 作者:quiller
字体大小
- | +

quiller下面一则新闻讨论了Vit B 在治疗Chronic pain(CP)方面的研究进展,非常好,并对治疗机制进行了推理。
目前这方面的研究不多,主要是因为治疗机理不明,很难建立合适的疼痛动物模型,最近动物模型有一定进展。
但临床上的应用早已开始,特别是在日本市场,复合Vit B(VBC)治疗慢性痛,已取得不殊的业绩。
最近,可以看到其它药物在治疗CP副作用报道越来越多,因此VBC的作用应被大家重视!

希望有兴趣者就此展开讨论!
==============================
Parker College Researchers Say Answer to Chronic Pain May Start With B-Vitamins
New Findings Reveal That This Treatment Could Be Highly Effective In Alleviating Pain Caused By Injury to the Nervous System

DALLAS, April 14 /PRNewswire/ -- Chronic pain affects some 86 million Americans a year and accounts for about $90 billion lost annually due to sick time, reduced productivity, and direct medical and other benefit costs. Many who suffer from chronic pain are told to learn to "live with it." Now new research indicates that relief may be found at the vitamin counter in your neighborhood grocery story.
Researchers in the Research Institute at Parker College of Chiropractic in Dallas, Texas, say they may have found an effective treatment for various painful conditions caused by injuries to the nervous system. Tests using B-vitamins, such as B1, B6, and B12, are showing significant results in blocking pain in laboratory rats.
Xuejun Song MD, PhD, Associate Professor and Associate Director of Basic Science Research, and Zhengbei Wang, MD, Postdoctoral Associate, both from the Parker Research Institute, are presenting their findings this week at the Experimental Biology meeting in San Diego (April 11-15, 2003) held by The American Physiological Society (APS) and the other five prestigious national research organizations. APS has identified the Parker team's study--one of thousands submitted from worldwide scientists--as one of the twelve that may hold potential interest for the public.
Dr. Song heads the research team, which conducted tests ranging 2-12 weeks to examine the short- and long-term effects of B-vitamins on rats that had been put through invasive operative procedures. The team's results found that both severity and duration of pain in these rats were significantly reduced depending on the dosage. "These studies strongly support and broaden the knowledge and clinical use of B-vitamins in aiding in treatment of chronic pain due to the nerve injury or spinal cord trauma and/or other injuries and diseases of the nervous systems," noted Song.

其中 Methyl B12的作用机理已有很多文章描述,它主要是通过修复受损伤的神经组织来达到治疗的目的:
1)容易高浓度地转运入神经细胞细胞器;(Inada et al. 1981)
2) 增强神经细胞内核酸和蛋白质的合成;(Nakazawa et al,1970)
3) 促进轴浆转运;( Takenaka,1982; Saito et al, 1981)
4) 促进髓鞘形成物质-磷脂的合成;(Yonezawa T. et al. 1981; Nakazawa T. et al, 1981)
5) 促进轴突的再生;(Onishi A. et al, 1979)
6) 加快突触传递的早期恢复;(Shibuya et. al, 1981)
7) 恢复被减少的神经传递物质。(Sasaki et al.,1992)

在日本有两个很知名的OTC产品,alinamin(武田),nabolin(卫材),主要成分都是B1、B2、B12(30mg/30mg/0.5mg),他们的功效都是缓和关节痛、神经痛、肩痛、腰痛、眼疲劳等症状,作为止痛的辅助治疗药物,已被许多患者接受。
不知我们国内的医生对这种药物组合的评价是怎样的?

神经性疼痛

  即使保守地估计,世界每年被诊断为糖尿病性神经病、疱疹后神经病和三叉神经痛的患者数亦有1400多万人。神经性疼痛还包括脊髓损伤、多发性硬化病、幻肢疼痛、中风后疼痛和艾滋病相关疼痛等。如果再加上神经性相关慢性背痛、骨关节炎和肿瘤所致疼痛,则全球遭受神经性疼痛困扰人数至少有3000万人。遗憾的是,现今尚无一药对50%神经性疼痛患者有效,故此疼痛治疗领域亟待开发疗效更好的新药。

我们国内的临床医生是如何处理这些问题的呢?

这段是Snoopyillness的分析,觉得很好,不知大家是否有共鸣,转摘于此:

维生素类:是治疗DPN最基本、应用最早的药物。正常神经组织主要依靠糖代谢供应能量,当维生素B族缺乏,糖代谢障碍,能量供应减少,神经组织最易受累。有报道DM患者血清中维生素B1浓度是低值,可能存在维生素B1缺乏的糖代谢障碍,而出现感觉异常等周围神经炎症状。给予维生素B1症状可得到改善,用100~200mg/d,im,或20mg,po,tid。亦有人提出维生素B12和碳水化合物与脂肪代谢紊乱,血液中谷胱苷肽浓度的减低等有关。因而DM患者有潜
在维生素B12缺乏,故用维生素B12治疗有效,250~500μg,im,qd。近年来采用的新制剂甲钴胺(弥可保)为一种活性维生素B12制剂。用甲钴胺治疗124例DPN患者,采用前4周500μg/次,im,2次/周;后8周500μg/次,po,tid。结果注射4周后症状和体征即改善,继续口服8周后改善更明显,运动和感觉NCV明显提高,并维持至12周。疗程中仅7例有轻微副作用,未影响疗程。临床研究证实甲钴胺口服和肌肉注射均能明显改善周围神经症状,而且能改善自主神经症状,并能明显提高NCV,是治疗DPN的一种安全有效的药物,具有肌肉注射起效快、口服方便且副作用极低,并能维持疗效的特点。甲钴胺与脱氧核苷维生素B12同为活性维生素B12,与非活性维生素B12(氰钴胺)相比,更易进入神经细胞内。甲钴胺是蛋氨酸合成酶的辅酶,此酶对神经细胞内合成用于组成轴突的结构蛋白至关重要;其另一重要作用是促进髓鞘的主要组成成分卵磷脂的合成,后者是一种重要磷脂,与髓鞘、核糖体膜、线粒体膜、突触及受体等的功能有关。故补充甲钴胺有利于DPN损伤神经的修复。

这样的理论我们医生是否可以接受:

日常生活中,肩和腰痛的最常见的三大原因:
肌肉僵硬:
肩和腰负担重时,从肌肉中产生的疲劳物质就会聚集起来。于是骨肉僵硬起来。
血液循环不畅通:
肌肉变得硬的话,血管被压迫,血液循环变得不畅通。于是疲劳物质不易排除,越发肌肉僵直。然而,血液循环不畅通,冷也伴随。
末梢神经障碍:
肌肉僵硬,更加压迫末梢神经。末梢神经因为传递着「痛的」「发麻」的刺激,末梢神经被压迫,有刺激的地方,就会觉得疼痛和发麻。疼痛和发麻,是末梢神经的状态恶化了的证据。这时,维生素B12和叶酸,在体内合成构成着末梢神经的蛋白质和脂体,要末梢神经补充正常的状态。

这篇最新的研究表明,加入VB12后,治疗Breast cancer,在改善疼痛和恶心方面有明显的提高!

Clin Breast Cancer. 2005 Jun;6(2):143-9. Related Articles, Links


Phase II Study of Pemetrexed in Patients Pretreated with an Anthracycline, a Taxane, and Capecitabine for Advanced Breast Cancer.

O'shaughnessy JA, Clark RS, Blum JL, Mennel RG, Snyder D, Ye Z, Liepa AM, Melemed AS, Yardley DA.

Texas Oncology, PA, and US Oncology, Dallas, TX; e-mail: joyce.o'shaughnessy@usoncology.com.

Background: This phase II study evaluated the efficacy, safety, and health outcomes of pemetrexed treatment in heavily pretreated patients with advanced breast cancer. Patients and Methods: Women with metastatic breast cancer, Karnofsky performance status >/= 70, and previous treatment with >/= 3 regimens containing anthracyclines, taxanes, and capecitabine were eligible. Pemetrexed 500 mg/m2 intravenous infusion was administered on day 1 of a 21-day treatment cycle. Results: Eighty patients were enrolled, and 60 received concurrent folic acid and vitamin B12 supplements per protocol amendment to minimize possible pemetrexed-related toxicity. The median numbers of cycles delivered were 3 for vitamin-supplemented patients and 2 for non-vitamin-supplemented patients. Regardless of vitamin supplementation, the overall response rate was 8% (95% CI, 3%-16.6%), stable disease was exhibited in 36% of patients, median time to disease progression was 2.9 months, and median survival was 8.2 months. Improvements in patient-reported symptoms ranged from 16.2% for pain intensity to 32.1% for nausea. Major grade 3/4 toxicities were hematologic, with grade 4 neutropenia in 10% of patients and grade 3 toxicities consisting primarily of neutropenia (29%) and leukopenia (21%). There were no clear trends of the effect of supplementation on toxicity. Conclusion: Pemetrexed has modest antitumor activity and is well tolerated in heavily pretreated patients with breast cancer. Further evaluation of this multitargeted antifolate in advanced breast cancer is warranted.


复合VB如何抑制由神经损伤或炎症引起的疼痛或痛觉过敏,其机理还不明白。然而,有些研究提供的证据可以用来做一些假设。
1)复合VB在轴突传导中的作用对快速止痛有积极的影响,这种观点已有很多试验研究(Itokawa and Cooper,1970;Takeshige et al., 1971);
2)长时间的抑制作用与复合VB之间的相互作用有关(Bernstein, 1990; Brennan et al., 1980; Healton et al., 1991; Leklem et al., 1999; Misra et al., 1977; laitakis, 1978);
3)在复合VB介导的止痛机制中,可能与cGMP信号通道相关(Vesely et al., 1985; Vocci et al., 1978; Abacioglu et al., 2000; Song and Wang, 2003);
4)Glutamate and calcium 通道对神经的传导都非常重要,可能与B6介导的痛觉抑制有关,B6可以改变细胞内glutamate 水平和细胞膜中calcium 水平(Dakshinamurti et al., 2003);
5)复合VB参与损伤神经的重建活动对神经功能的恢复和缩短疼痛时间有积极的影响(Fujii et al., 1996)。

jiangyq77维生素类
维生素类作为神经系统损伤后修复过程中的辅酶类物质,对维持神经系统正常生理功能有极重要的作用,所以在临床上不论对于神经损伤产生的神经系统结构或功能异常还是因神经系统受到各种因素的刺激发生功能紊乱的治疗中都具有重要的意义。是我们慢性疼痛临床治疗中维生素类最常使用的药物之一。
1、维生素B1
VB1是糖类代谢所必需的物质,在体内与焦磷酸结合成转羧酶,主要参与糖代谢中丙酮酸和X-酮戊二酸的氧化脱羧反应。VB1缺乏时氧化过程受阻,大量的丙酮酸、乳酸在体内堆积,明显影响机体能量供应和各项生理功能的正常进行。
2、维生素B6
VB6在红细胞内转化为具有生理活性的吡多醇、磷酸吡多醛,参与细胞色素的合成。作为转酶对蛋白蛋、碳水化合物、脂肪的各种代谢功能作用,还参与色氨酸转化,将烟酸转化为5-羟色胺。脑内的γ-氨基丁酸由谷氨酸脱羧而成,有调节大脑兴奋性的作用,故缺乏维生素B6的患者,可导致不安,应激性增加,抽搐等中枢兴奋状态。与维生素B12合用,可促进维生素B12的吸收。
3、维生素B12
VB12为一种含钴的红色化合物,作为辅酶参与体内许多生化代谢反应,具有广泛的生理作用,但是需转化为甲基钴胺和辅酶B12后才具有活性,VB12能促进甲基丙二酸变成琥珀酸,从而对神经髓鞘中脂蛋白的形成,保护中枢和外周的有髓神经纤维的功能完整性起重要作用。VB12对神经亲和力强,有修复神经髓鞘、促进再生作用,缺乏时可引起脑、脊髓和外周神经变性,脂酸代谢障碍。
4、口服药物
弥可保(甲钴胺)片;
维生素B类;
复方维生素类;
5、注射剂
弥可保(甲钴胺)注射液;
维生素B类:B1、B12。

再附上一篇相关外文文献,有点老了,呵呵
Schmerz. 1998 Apr 20;12(2):136-41
Analgesic and analgesia-potentiating action of B vitamins
Jurna I.
Medizinische Fakultat der Universitat des Saarlandes, Homburg/Saar.

Disregarding pain resulting from vitamin deficiency, an analgesic effect seems to be exerted only by vitamin B1 (thiamine), vitamin B6 (pyridoxines), and vitamin B12 (cobalamine), particularly when the three are given in combination. The analgesic effect is attributed to an increased availability and/or effectiveness of noradrenaline and 5-hydroxytryptamine acting as inhibitory transmitters in the nociceptive system.In animal experiments, high doses of these vitamins administered alone or in combination inhibited nociceptive behavior and depressed the nociceptive activity evoked in single neurons of the dorsal horn of the spinal cord and in the thalamus. Moreover, they were found to enhance the antinociceptive effect of non-opioid analgesic agents on withdrawal reflexes. Clinical data fail in most cases to meet current standards of evaluation (randomization, double-blindness). Still, it appears that high doses of the vitamins B1, B6, and B12 administered separately or in combination can alleviate acute pain and potentiate the analgesia caused by non-opioid analgesics such as the NSAIDs and metamizol (dipyrone). Therapeutic effects are observed in neuropathic pain and pain of musculoskeletal origin. Vitamin B6 is effective in the carpal tunnel syndrome which, however, is attributed at least in some cases to vitamin B6 deficiency. It is also worth noting that the B vitamins are shown to enhance the beneficial effect of diclofenac in acute low-back pain so that either the duration of treatment or the daily dose of diclofenac may be reduced. The use of high doses of vitamin B6 may be limited by a neurotoxic effect. The effectiveness of B vitamins in depressing chronic pain has not been established. It would be interesting to know if the B vitamins are of use as adjuvants in the treatment of tumor pain.


quiller美国人疼痛问题

由美国《ABC新闻》和“今日美国&斯坦福大学医学研究中心”共同主持的一项研究结果表明,超过半数的美国人患有慢性或反复性的疼痛症,而且大多数人表示疼痛症影响到了他们的情绪、睡眠以及日常生活的方方面面。
据调查,将近五成的受访者在过去两周内有过明显的疼痛感,而且约四成的受访者称他们会经常疼痛。另外,40%的受访者上一次的疼痛属于中度疼痛,20%的受访者上一次的疼痛很严重;19%的受访者表示他们一直饱受慢性疼痛(指持续三个月及以上的疼痛)的煎熬,34%的受访者称他们患有反复性疼痛症,还有44%称他们的疼痛是急性的、短期的。

疼痛的位置主要集中在背部,膝盖和头部。四分之一的受访者说他们上一次的疼痛发生在背部。也就是说背部疼痛以25%的比例“雄居榜首”,远远超过排在第二位的膝盖痛(12%)、第三位的头痛或偏头痛(9%)、第四位的肩膀痛及腿痛(均为7%)。这四个部位的疼痛占受访者所反映的所有部位疼痛的60%。
疼痛给人们的生活带来了很多不利影响。疼痛患者对生活的总体满意度低于总体平均水平。另外,四成左右的人表示疼痛影响到了他们的心理状态、睡眠以及日常生活的方方面面;还有24%的人认为疼痛还影响到了他们与其它人的关系。
为了解除疼痛,人们想尽了办法。服用非处方药以及采取一些家用的治疗措施(如使用热垫子、冰袋、洗热水澡等)是美国人常用的治疗方法,约80%的人尝试过以上方法;约有60%的人通过服用处方药、卧床休息以及做祷告的方式减轻病痛。采取其它方式解除疼痛的人数比率明显低于以上这几种方法:28%的人作按摩,16%的人服用草药,14%的人去做瑜珈,12%的人通过喝酒减轻病痛,6%的人选择抽烟,还有5%的人选择针灸来治疗疼痛。


编辑: Zhu

版权声明

本网站所有注明“来源:丁香园”的文字、图片和音视频资料,版权均属于丁香园所有,非经授权,任何媒体、网站或个人不得转载,授权转载时须注明“来源:丁香园”。本网所有转载文章系出于传递更多信息之目的,且明确注明来源和作者,不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。同时转载内容不代表本站立场。