B族维生素在治疗慢性疼痛中的地位及作用机制讨论.doc
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B族维生素在治疗慢性疼痛中的地位及作用机制讨论
转载自丁香园网站
文中讨论了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.......（后略) ......
B族维生素在治疗慢性疼痛中的地位及作用机制讨论
转载自丁香园网站
文中讨论了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.......（后略) ......
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