【原创】B族维生素在治疗慢性疼痛中的地位及作用机制讨论
**** Hidden Message ***** **** Hidden Message ***** **** Hidden Message ***** 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。 临床研究：这项研究纳入135例病人，分两组，一组应用大剂量的甲钴胺，时间为2年。电生理学研究表明，口服钴胺素治疗对脑卒中CTS有益处，并且安全。
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J Neurol Sci. 2005 Apr 15;231(1-2):13-8. Epub 2005 Jan 16.
Amelioration by mecobalamin of subclinical carpal tunnel syndrome involving unaffected limbs in stroke patients.
甲钴胺在减轻脑卒中病人的亚临床腕管综合症相关的上肢障碍中的作用
Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K.
Department of Neurology, Mitate Hospital, 3237 Yugeta, Tagawa 826-0041, Japan. [email]y-sato@ktarn.or.jp[/email]
Our previous study showed that overuse of the nonparetic hand and wrist of the nonparetic side following stroke result in significantly more abnormal on the nonparetic side than on the hemiparetic side in terms of electrophysiologic indices of median nerve function. The purpose of this study was to evaluate the effects of the orally administered mecobalamin, an analogue of vitamin B12, for carpal tunnel syndrome (CTS) in the nonparetic side in patients following stroke. In a randomized open label and prospective study of stroke patients, 67 received of 1500 mug mecobalamin daily for 2 years, and the remaining 68 (untreated group) did not. At baseline, sensory nerve conduction velocity, motor nerve conduction velocity, sensory nerve action potentials (SNAP) at the wrist, palm-to-wrist distal sensory latency, palm-to-wrist SNAP, motor nerve conduction velocity compound motor action potentials, and distal motor latency of median nerve were significantly more abnormal on the nonparetic side than on the hemiparetic side or in controls. Before the treatment 21 patients (31%) of untreated and 20 patients (30%) of treated group met electrophysiologic criteria for CTS. Sensory impairment of the nonparetic side had lessened in the treated group. After 2 years, all electrophysiologic indices of nonparetic side were significantly improved in the treated group compared with those in the untreated group.
The improvement from baseline of electrophysiologic parameters in sensory nerve in the treated group was greater than the improvement measured in motor nerve. There were no side effects. Oral mecobalamin treatment is a safe and potentially beneficial therapy for CTS in stroke patients. 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'[email]shaughnessy@usoncology.com[/email].
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. VB12在糖尿病神经病变中的作用:临床试验综述
VB12及其活性物质对糖尿病性神经病变的疗效现在还不是非常明确。我们检索了英文和非英文的文献，在1954年到2004年有7个随机临床试验，比较分析认为，无论是VB12还是其活性物质对病情的改善都有很大的提高。
Acta Neurol Taiwan. 2005 Jun;14(2):48-54. Related Articles, Links
Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials.
Sun Y, Lai MS, Lu CJ.
Department of Neurology, En Chu Kong Hospital, No. 399, Fuhsin Road, San-shia, Taipei, Taiwan. [email]sunyu@ms4.hinet.net[/email]
The clinical effectiveness of vitamin B12 and its active coenzyme form on diabetic neuropathy is uncertain. Therefore, we searched the English- and non-English-language literature on this topic by using MEDLINE (Ovid, PubMed), the Cochrane Controlled Trials Register, and related papers. We identified seven randomized controlled trials from June 1954 to July 2004 and reviewed them for the clinical effectiveness of vitamin B12 according to the following parameters: Measurement scales of somatic and autonomic symptoms or signs; vibrometer-detected thresholds of vibration perception; and, electrophysiologic measures such as nerve conduction velocities and evoked potentials. Three studies involved the use of vitamin B complex (including B12) as the active drug, and four used methylcobalamin. Two studies were of fairly good quality (Jadad score = 3/5), and five were of poor quality (Jadad score < or = 2/5). Both the vitamin B12 combination and pure methylcobalamin had beneficial effects on somatic symptoms, such as pain and paresthesia. In three studies, methylcobalamin therapy improved autonomic symptoms. Effects on vibration perception and electrophysiological measures were not consistent. With both the vitamin B12 combination and pure methylcobalamin, symptomatic relief was greater than changes in electrophysiological results. However, more high-quality, double-blind randomized controlled trials are needed to confirm the effects of vitamin B12 on diabetic neuropathy.
PMID: 16008162 [PubMed - in process] Eur Rev Med Pharmacol Sci. 2000 May-Jun;4(3):53-8. Related Articles, Links
Vitamin B12 in low back pain: a randomised, double-blind, placebo-controlled study.
Mauro GL, Martorana U, Cataldo P, Brancato G, Letizia G.
Clinica Ortopedica e Traumatologica con Fisioterapia e Medicina dello Sport, Universita degli Studi di Palermo, Italy.
OBJECTIVES: 这项双盲、随机化、安慰剂研究目的是将审查注射维生素B12 (Tricortin 1000) 治疗后背痛病人中的效果和安全性。
方法: 60 名患者，年龄在18 到65 岁，以腰痛或臀部的神经炎机械起源，没有进行外科手术病人纳入。患者必须出席以被证明的病史为背部疼痛(持续从6 个月到5 年) 并且痛苦强度[ 依照被评估与一个视觉类推标度(VAS) ] 均等或大于60 毫米。效力主要终点被评估了a Visual Analogic Scale (VAS) 并且伤残查询表(DQ)。
paracetamol 的消耗量在研究期间是次要效力终点。
结果: 治疗小组体验了在痛苦和伤残的急剧减退。但是, 比较在小组之间在治疗期间的结尾显示出一个统计地重大区别倾向于活跃治疗为VAS 和DQ (p < 0.0001 and p < 0.0002, respectively)。在安慰剂小组比在活跃治疗组，paracetamol 的消耗量显显著增高。
结论: 在没有营养缺乏的患者，辅以肠外维生素B12治疗，在缓和腰酸和相关伤残和减少paracetamol 的消耗量，证实了肠外维生素B12 效果和安全。 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. 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。 维生素B12 治疗糖尿病性神经病变的疗效：对照临床试验系统评价
Acta Neurol Taiwan. 2005 Jun;14(2):48-54.
摘要与简评：台湾神经科医生检索了MEDLINE, Cochrane 注册对照试验及相关数据库中收录的维生素B12 治疗糖尿病性神经病变随机、对照临床试验文献，并进行了系统评价。共检索到1954-2004 年发表的随机、对照试验文献7 篇：3 项临床试验使用复合维生素(包括普通维生素B12)，4 项临床试验使用甲钴胺治疗糖尿病性神经病变。疗效评价指标包括躯体或自主神经症状评分、振动知觉阈值和电生理检查结果（如神经传导速度和诱发电位）。
结果显示，
1）普通维生素B12 和甲钴胺均能有效改善糖尿病性神经病变躯体神经症状，如疼痛和感觉异常；
2）3 项临床试验结果显示，甲钴胺治疗能改善糖尿病性神经病变自主神经症状；
3）普通维生素B12 和甲钴胺对糖尿病性神经病变症状的改善程度强于对神经电生理指标的改善。
现在的医学模式正在经历从经验医学到循证医学的转变。循证医学中的证据按质量和可靠程度可分为五级（可靠性依次降低）。
一级：所有随机对照试验(randomized controlled trials，RCT)的系统评价/Meta-分析。
二级：单个的样本量足够的RCT 结果。
三级：设有对照组但未用随机方法分组。
四级：无对照的病例观察。
五级：专家意见。
在治疗方面，国际公认大样本随机对照试验（RCT）和RCT 的系统评价（systematic review SR，或Meta-分析）结果是证明某种疗法的有效性和安全性最可靠的依据（金标准）。
根据循证医学的分类，这篇系统评价属于一级证据，对临床实践具有指导意义。
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