这是用户在 2024-6-14 13:39 为 https://app.immersivetranslate.com/pdf-pro/48a55cb6-9685-4ba4-9d92-33bce92350b2 保存的双语快照页面，由 沉浸式翻译 提供双语支持。了解如何保存？
2024_06_04_45f147dde876338f4042g

Double-blind, multicenter trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients
比较乙酰左旋肉碱和安慰剂治疗纤维肌痛患者的双盲多中心试验

M. Rossini , O. Di Munno², G. Valentini , G. Bianchi , G. Biasi , E. Cacace ,
M.Rossini , O. Di Munno², G. Valentini , G. Bianchi , G. Biasi , E. Cacace 、D. Malesci , G. La Montagna , O. Viapiana , S. Adami
D.Malesci , G. La Montagna , O. Viapiana , S. Adami

Rheumatology Unit, University of Verona; Rheumatology Unit, University of Pisa;
维罗纳大学风湿病科； 比萨大学风湿病科； Rheumatology Unit, University of Naples; Rheumatology Unit, Ospedale "La Colletta",
那不勒斯大学风湿病科； "La Colletta "医院风湿病科、Arenzano; Rheumatology Unit, University of Siena; Rheumatology Unit, University of
Arenzano； 锡耶纳大学风湿病学组； 锡耶纳大学风湿病学组Cagliari, Italy. 意大利，卡利亚里

Abstract

Objective

Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue. Several analgesic strategies have been evaluated but the results are moderate and inconsistent. Antidepressant agents are now considered the treatment of choice in most patients. It has been recently suggested that FMS may be associated with metabolic alterations including a deficit of carnitine. In this multicenter randomized clinical trial we evaluated the efficacy of acetyl L-carnitine (LAC) in patients with overt FMS.
纤维肌痛（FMS）是一种以广泛性疼痛、睡眠障碍、情绪紊乱和疲劳为特征的慢性综合征。目前已对几种镇痛策略进行了评估，但效果一般且不一致。目前，抗抑郁剂被认为是大多数患者的首选治疗方法。最近有研究表明，FMS 可能与包括肉碱缺乏在内的新陈代谢改变有关。在这项多中心随机临床试验中，我们评估了乙酰左旋肉碱（LAC）对明显 FMS 患者的疗效。

Methods

One hundred and two patients meeting the American College of Rheumatology criteria for FMS were randomized into the study. The treatment consisted of 2 capsules/day of LAC or placebo plus one intramuscular (i.m.) injection of either LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either LAC or placebo. The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit). Outcome measures included the number of positive tender points, the sum of pain threshold ( or "total myalgic score"), the Short Form 36 (SF36), a 100 mm visual analog scale (VAS) for self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain, and the Hamilton depression scale.
符合美国风湿病学会 FMS 标准的 112 名患者被随机纳入研究。治疗包括每天服用2粒 LAC或安慰剂，外加1次 LAC或安慰剂肌肉注射（i.m.），持续2周。在随后的 8 周内，患者每天服用 3 粒含 LAC 或安慰剂的胶囊。在治疗期间，患者分别在 2 周（第 3 次就诊）、6 周（第 4 次就诊）和 10 周（第 5 次就诊）后就诊。停药4周后（随访）也对患者进行了随访。结果测量包括阳性触痛点数量、疼痛阈值总和（ 或 "肌痛总分"）、简表36（SF36）、100毫米视觉模拟量表（VAS），用于测量自我感觉的僵硬、疲劳、觉醒时的疲倦、睡眠、工作状态、抑郁和肌肉骨骼疼痛，以及汉密尔顿抑郁量表。

Results

The "total myalgic score" and the number of positive tender points declined significantly and equally in both groups until the week of treatment. At the week both parameters remained unchanged in the placebo group but they continued to improve in the LAC group with a statistically significant between-group difference. Most VAS scores significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain. Significantly larger improvements in SF36 questionnaire were observed in LAC than in placebo group for most parameters. Treatment was well-tolerated.
在治疗的 周之前，两组的 "肌痛总分 "和阳性触痛点的数量均有显著下降。在 周，安慰剂组的这两项参数保持不变，但LAC组则继续改善，组间差异有统计学意义。两组的大多数 VAS 评分均有明显改善。抑郁和肌肉骨骼疼痛的组间差异具有统计学意义。在大多数参数上，LAC 组 SF36 问卷的改善幅度明显大于安慰剂组。治疗耐受性良好。

Conclusion

Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.
尽管这一经验值得进一步研究，但这些结果表明，LAC 可能对 FMS 患者有益，可以改善这些患者的疼痛以及全身和心理健康。

Key words

Fibromyalgia, L-carnitine, pain.
纤维肌痛、左旋肉碱、疼痛

Maurizio Rossini, Ombretta Di Munno,
Introduction
莫里兹奥-罗西尼，Ombretta Di Munno，引言

Gabriele Valentini, Girolamo Bianchi, Giovanni Biasi, Enrico Cacace, Domenico Malesci, Giovanni La Montagna, Ombretta Viapiana, Silvano Adami.
Gabriele Valentini、Girolamo Bianchi、Giovanni Biasi、Enrico Cacace、Domenico Malesci、Giovanni La Montagna、Ombretta Viapiana、Silvano Adami。
Please address correspondence to: Prof. Silvano Adami, Rheumatologic Rehabilitation, University of Verona, Ospedale di Valeggio, 37067, Verona, Italy.
来信请寄Silvano Adami 教授，维罗纳大学风湿康复科，Ospedale di Valeggio，37067，维罗纳，意大利。
E-mail: silvano.adami@univr.it
电子邮件： silvano.adami@univr.it
Received on April 24, 2006; accepted in revised form on July 27, 2006.
2006年4月24日收到；2006年7月27日接受修订稿。
(C) Copyright CLINICAL AND
(C) 版权 临床和
EXPERIMENTAL RHEUMATOLOGY 2007. disorder (2).
EXPERIMENTAL RHEUMATOLOGY 2007.
Fibromyalgia (FMS) is a chronic syndrome characterized by widespread pain, troubled sleep, disturbed mood, and fatigue (1). It is estimated to be the second most common rheumatologic
纤维肌痛（FMS）是一种以广泛性疼痛、睡眠障碍、情绪紊乱和疲劳为特征的慢性综合征（1）。据估计，它是第二大最常见的风湿性疾病。
The cause of fibromyalgia has not been clearly defined, but several mechanisms may be involved. Abnormalities in muscle structure, and a variety of neurotransmitter and neuroendocrine changes may contribute to the de-velopment of fibromyalgia (3-5).
纤维肌痛的病因尚未明确，但可能涉及多种机制。肌肉结构异常以及各种神经递质和神经内分泌的变化都可能导致纤维肌痛的发生（3-5）。
A range of treatments are employed to treat the various symptom facets of FMS. These include neuromodulatory medications such as antidepressants, opioids, nonsteroidal antiinflammatory drugs, sedatives, muscle relaxants, and anti-epileptics, or nonpharmaceutical treatment modalities, including education, exercise, physical therapy, massage, and cognitive behavioral therapy (5-9). These therapies, both pharmacologic and nonpharmacologic, show only limited success, although drugs that affect serotonin or nor-epinephrine at the receptor site (such as antidepressants) seem to generate the most consistent results.
有一系列治疗方法可用于治疗 FMS 的各种症状。其中包括神经调节药物，如抗抑郁药、阿片类药物、非甾体抗炎药、镇静剂、肌肉松弛剂和抗癫痫药，或非药物治疗方式，包括教育、运动、理疗、按摩和认知行为疗法（5-9）。这些疗法，包括药物疗法和非药物疗法，都只取得了有限的成功，但影响血清素或非肾上腺素受体部位的药物（如抗抑郁药）似乎能产生最稳定的效果。
In recent studies it has been suggested that FMS may be associated with metabolic alterations contributing to the development of the syndrome (10). For example a deficit of carnitine has been suspected in fibromyalgic patients. Carnitine plays an important role in energy supply by controlling the influx of long-chain fatty acids into mitochondria. Disorders associated with carnitine deficiency may impair the function of liver, heart and skeletal muscle; clinically muscle carnitine de-ficiency is characterized by weakness, fatigue, and exercise intolerance that are important symptoms in FMS patients. In muscle biopsies from FM patients ragged red fibers have been found and a metabolic disturbance with low levels of high energy phosphates has also been demonstrated, but the content of carnitine was normal (11-13). Recently, however, a carnitine deficiency has been described in the skeletal muscle tissues of a subgroup of patients with FMS (14). There was also increased pyruvicemia and acylcarnitine/free carnitine ratio, indicating a deficit of carnitine (15). Lcarnitine may have a role in reducing the hypoxic stress of tissues: ischemia in endothelial cells can result in carnitine release, increased oxidative stress, and compromised blood flow; these responses can be ameliorated by carnitine administration (16).
最近的研究表明，纤维肌痛综合症可能与新陈代谢的改变有关，而新陈代谢的改变会导致该综合症的发生（10）。例如，有人怀疑纤维肌痛患者体内缺乏肉碱。肉碱通过控制长链脂肪酸流入线粒体，在能量供应方面发挥着重要作用。与肉碱缺乏有关的疾病可能会损害肝脏、心脏和骨骼肌的功能；临床上，肌肉肉碱缺乏的特征是虚弱、疲劳和运动不耐受，而这正是纤维肌痛患者的重要症状。在 FM 患者的肌肉活组织切片中，发现了红色的粗纤维，还发现了高能磷酸盐含量低的代谢紊乱，但肉碱含量正常（11-13）。然而，最近在一组 FMS 患者的骨骼肌组织中发现了肉碱缺乏症（14）。此外，丙酮酸血症和酰基肉碱/游离肉碱比值升高，表明肉碱缺乏（15）。左旋肉碱可能在减轻组织的缺氧压力方面发挥作用：内皮细胞缺血可导致肉碱释放、氧化应激增加和血流量减少；服用左旋肉碱可改善这些反应（16）。
This provides a reasonable rational for evaluating the effect of L-acetylcarnitine (LAC) therapy which is also known to exert a positive effect in the elderly with mood disturbances and depression (17-22). In this multicenter randomized clinical trial we evaluated the efficacy of LAC in patients with overt FMS.
这为评估左旋乙酰肉碱（LAC）疗法的效果提供了合理的依据，众所周知，左旋乙酰肉碱对患有情绪障碍和抑郁症的老年人也有积极作用（17-22）。在这项多中心随机临床试验中，我们评估了 LAC 对明显 FMS 患者的疗效。

Methods

Patients
Subjects were recruited from 7 rheumatology outpatient clinics in Italy. Enrolment began in January 2002 and the study was completed in June 2004. The patients were eligible for inclusion in the study if they were at least 18 years of age and met the American College of Rheumatology 1990 criteria for FMS (1). Patients were excluded if they had evidence of: any inflammatory disease involving bone, joints, enthesis or skin, symptomatic osteoarthritis; recent trauma; infectious or endocrine diseases; clinically unstable medical illness; a history of seizure, head trauma, or stroke; history of severe psychiatric conditions (hypomania, mania, psychosis, dementia); lifetime history of alcohol or drug dependence; use of antidepressants within 6 months before randomization or recent ( year) initiation of hormone replacement therapy; received non-steroidal antiinflammatory drugs or analgesic compounds within 3 and 7 days, respectively, before randomization; pregnant or fertile women not on contra- ception.
研究对象来自意大利的 7 家风湿病门诊诊所。研究于 2002 年 1 月开始，2004 年 6 月结束。年满 18 周岁且符合 1990 年美国风湿病学会 FMS 标准 (1) 的患者均可被纳入研究。以下情况的患者不在研究范围内任何涉及骨骼、关节、内脏或皮肤的炎症性疾病，有症状的骨关节炎；近期受过创伤；感染性疾病或内分泌疾病；临床病情不稳定；有癫痫发作、头部外伤或中风史；有严重精神病史（躁狂症、狂躁症、精神病、痴呆症）；终生有酒精或药物依赖史；随机分组前 6 个月内使用过抗抑郁药，或最近（ 年）开始接受激素替代治疗；随机分组前 3 天和 7 天内分别服用过非甾体抗炎药或镇痛化合物；未服用禁忌药物的孕妇或已育女性。

Outcome measurements 成果测量

Subjects were examined for the number of positive tender points by a "Pressure Threshold Meter", with a rubber disc of applied at a vertical angle to the 18 tender point sites (23). Pressure was progressively increased until subjects indicated verbally when they first felt discomfort. The pressure was
受试者使用 "压力阈值计 "检查阳性触痛点的数量，将一个 的橡胶圆盘以 的垂直角度贴在 18 个触痛点部位（23）。压力逐渐增加，直到受试者口头表示首次感到不适为止。压力为
then stopped and the weight read on the digitalized manometer. The individual scores were summed to give the "total myalgic score".
然后停止，用数字压力计读取体重。将单项得分相加得出 "肌痛总分"。
A visual analog scale (VAS) was used to evaluate self-perceived stiffness, fatigue, tiredness on awakening, sleep, work status, depression, and muscular-skeletal pain. The general health profile of the patients was assessed by the Short Form 36 (SF36) questionnaire and the typical 9 domain calculated separately (24). The 17 -item Hamilton scale was used for assessing depression (25). The screening protocol included an interview for demographic information; medical, psychiatric, and family history.
视觉模拟量表（VAS）用于评估自我感觉的僵硬、疲劳、觉醒时的疲倦、睡眠、工作状态、抑郁和肌肉骨骼疼痛。患者的一般健康状况由简表 36（SF36）问卷和分别计算的典型 9 个领域进行评估（24）。抑郁评估采用了 17 项汉密尔顿量表（25）。筛查方案包括人口统计学信息访谈、病史、精神病史和家族史。

Study treatment 研究治疗

The eligibility of the patients for the study was evaluated at the screening visit. The main inclusion criteria was the presence of at least 11 positive trigger points with pain defined as unbearable at a pressure .
患者的研究资格在筛查时进行评估。主要的纳入标准是至少有 11 个阳性触发点，且在按压 时疼痛难以忍受。
After the screening visit, the patients were invited to discontinue any chronic treatment with non-steroidal anti-inflammatory or analgesic drugs and invited to attend the randomization visit 7 days later (visit 2). The randomization code was obtained by phone according to a randomization list for either -acetylcarnitine (LAC) or placebo in a 1:1 ratio. Treatment was double blind and double dummy throughout. The treatment was 2 capsules/day of LAC or placebo plus one intramuscular (i.m.) injection of either LAC or placebo for 2 weeks. During the following 8 weeks the patients took 3 capsules daily containing either LAC or placebo. All formulations for both active and placebo were prepared and provided by Sigma Tau (Pomezia, Rome, Italy).
筛查结束后，患者被邀请停止任何非甾体抗炎药或镇痛药的长期治疗，并被邀请参加7天后的随机检查（第2次检查）。随机化代码是根据随机化名单通过电话获得的， -乙酰肉碱（LAC）或安慰剂的比例为1:1。整个治疗过程均为双盲双假。治疗方法是每天服用2粒 -乙酰肉碱或安慰剂，外加1次 -乙酰肉碱或安慰剂肌肉注射（i.m.），持续2周。在随后的 8 周内，患者每天服用 3 粒含 LAC 或安慰剂的胶囊。活性药物和安慰剂的所有配方均由 Sigma Tau 公司（意大利罗马，Pomezia）制备和提供。
The patients were seen during treatment after 2 (visit 3), 6 (visit 4) and 10 weeks (visit 5). The patients were also visited 4 weeks after treatment discontinuation (follow-up visit).
在治疗期间，患者分别在 2 周（第 3 次就诊）、6 周（第 4 次就诊）和 10 周（第 5 次就诊）后就诊。停药 4 周后，还对患者进行了随访。
The "total myalgic score" that was obtained at all visits, was the primary end point of the study. The Hamilton test was performed at visit 2,3 and 5, while all VAS scores and the SF 36 questionnaire were assessed only at the screening visit and at visit 5 (end of treatment): all these outcomes were secondary end points of the study.
在所有检查中获得的 "肌痛总分 "是研究的主要终点。汉密尔顿测试在第 2、3 和 5 次就诊时进行，而所有 VAS 评分和 SF 36 问卷仅在筛查就诊和第 5 次就诊（治疗结束）时进行评估：所有这些结果都是研究的次要终点。
The study protocol was approved by the local Ethics Committee and all subjects provided written informed consent.
研究方案获得了当地伦理委员会的批准，所有受试者都提供了书面知情同意书。

Statistical analysis 统计分析

The study was designed to enrol 100 patients in order to detect a treatment group difference of in the "total myalgic score" with a power. The difference was based on the wish to power this study to demonstrate a clinically meaningful effect.
该研究旨在招募 100 名患者，以 的功率检测治疗组在 "肌痛总评分 "方面的 差异。这一差异是基于希望这项研究能够证明具有临床意义的效果。
The statistical significance of changes from baseline was determined using the paired -test. Differences in outcome parameters response were calculated using analysis of covariance (ANCOVA) with Bonferroni test for adjusting significance to multiple com- parisons and with pretreatment drug as the factor and the corresponding baseline parameter values as the covariate. The primary analysis was by intentionto-treat, without regard to adherence, applied to patients in whom at least one post-treatment evaluation was obtained. We computed outcomes for patients with missing measurements by carrying forward the most recent postenrolment measurement (last observation carried forward).
采用配对 检验确定与基线相比变化的统计学意义。采用协方差分析（ANCOVA）计算结果参数反应的差异，并采用Bonferroni检验调整多重比较的显著性，以治疗前的药物作为因素，相应的基线参数值作为协变量。主要分析采用意向治疗，不考虑依从性，适用于至少获得一次治疗后评估的患者。对于测量结果缺失的患者，我们通过转入最近的入组后测量结果（转入的最后一个观察结果）来计算其结果。

Results

One hundred and two patients were enrolled and randomized to receive study treatment by an automatic procedure. Three of these patients were male. During a post-enrollment evaluation of the Clinical Research Forms by the Contract Research Organization (CRO), 7 patients were excluded either for violation of inclusion-exclusion criteria or
112 名患者通过自动程序注册并随机接受研究治疗。其中 3 名患者为男性。在合同研究组织（CRO）对临床研究表格进行注册后评估期间，有 7 名患者因违反纳入-排除标准或
Fig 1. Diagram of patient flow. The diagram represents the outcome of all patients who entered the study. ITT intent-to-treat; per-protocol.
图 1.患者流程图。该图表示所有参与研究的患者的结果。ITT 意向治疗； 按方案治疗。
because after enrolment they continued non allowed therapies. Six patients did not attend the first post-treatment visit, thus leaving the number of patients available for the ITT analysis at 42 and 47 for LAC and placebo respectively (Fig. 1). Fourteen patients were then lost to follow-up and the final number of patients left for a per protocol analysis (PP) were 38 and 37 for LAC and placebo, respectively. Seven additional patients did not attend the post-treatment follow-up visit.
因为他们在入组后继续接受非允许疗法。有 6 名患者没有参加治疗后的首次随访，因此可用于 ITT 分析的患者人数分别为 42 人（LAC）和 47 人（安慰剂）（图 1）。随后又有 14 名患者失去了随访机会，最终可用于按方案分析（PP）的患者人数分别为 38 人（LAC）和 37 人（安慰剂）。另有 7 名患者没有参加治疗后的随访。
The main baseline characteristics of the study population are listed in Table I. The two groups were comparable for all characteristics by considering both the ITT (Table I) and the PP population (data not shown).
研究对象的主要基线特征列于表 I。通过考虑 ITT（表 I）和 PP 组人群（数据未显示），两组人群的所有特征均具有可比性。
The changes in the primary end point of the study, the total myalgic score over time are illustrated in Figure 2. The score declined significantly and equally in both groups until the week of treatment. At the week the score remained unchanged in the placebo group but it continued to improve in the LAC group with a statistically significant between-group difference. A similar pattern of changes was observed in the mean number of positive ( pain threshold) tender points, with a significant between-treatment difference at week 10 both for the absolute number (Fig. 2, lower panel) and with regards to its change ( 0.02; data not shown). By analyzing the PP study population most of the significance either did not change or improved.
图 2 显示了研究的主要终点--肌痛总分随时间的变化。在治疗的 周之前，两组的得分均有明显下降。在 周，安慰剂组的得分保持不变，但LAC组的得分继续提高，组间差异有统计学意义。阳性（ 痛阈值）触痛点的平均数量也出现了类似的变化，在第10周时，无论是绝对数量（图2，下图）还是其变化（ 0.02；数据未显示），治疗组之间都存在显著差异。通过对PP研究人群进行分析，大多数显著性要么没有变化，要么有所改善。
The changes in VAS score for subjective symptoms from baseline to the end of the treatment are illustrated in Figure 3. With the exception of depression in the placebo group, all other items significantly improved in both groups. A statistically significant between-group difference was observed for depression and musculo-skeletal pain.
图 3 显示了主观症状 VAS 评分从基线到治疗结束的变化情况。除安慰剂组的抑郁外，两组的其他项目均有明显改善。抑郁和肌肉骨骼疼痛的组间差异具有统计学意义。
The changes in the main domains of the SF36 questionnaire are shown in Figure 4. A significant improvement was observed in 7 out of 10 parameters and in 3 out 10 in the LAC and placebo group respectively. A significant between-group difference was observed for bodily pain, mental health, general
图 4 显示了 SF36 问卷主要领域的变化。在 10 个参数中，LAC 组和安慰剂组分别有 7 个和 3 个参数有明显改善。在身体疼痛、精神健康、一般健康和心理健康方面，观察到了明显的组间差异。
Table I. Mean baseline clinical characteristics (standard deviation) of the patients who had at least one post-treatment evaluation (ITT group).
表 I.至少接受过一次治疗后评估的患者（ITT 组）的平均基线临床特征（标准偏差）。
Placebo  安慰剂
Age (years)
Height (cm)
Weight  重量
BMI
Mean tender point threshold
平均触痛点 阈值
Mean number positive tender points
阳性 触痛点的平均数量
, range
, 范围
Physical functioning 身体机能
Social functioning 社会功能
Role limitation - physical
角色限制--身体
Bodily pain
Mental health
Role limitation- emotional
角色限制--情感
Vitality
General Health perception
一般健康观念
Visual Analog Scale (1-100)
视觉模拟量表（1-100）
Stiffness
Fatigue
Tiredness on awakening 醒来时感到疲倦
Sleep disturbances 睡眠障碍
Pain and daily activities
疼痛与日常活动
Depression
Muscolo-skeletal pain 肌肉骨骼疼痛
Hamilton Rating Scale
汉密尔顿分级量表
Fig. 2. Mean changes in pain threshold (pressure threshold meter, ) and number of positive tender points over time.
图 2.疼痛阈值（压力阈值计， ）和阳性触痛点数量随时间的平均变化。
health perception and both mental and physical total scores.
健康感知以及心理和生理总分。
The longitudinal changes in the Ham- ilton score are shown Figure 5. The mean score was approximately 12 in both groups, far below the 15-20,
汉密尔顿评分的纵向变化如图 5 所示。两组的平均得分均为 12 分左右，远低于 15-20 分的标准、
which represents the minimum score for a longitudinal evaluation (26) The mean score significantly improved in the LAC group at week 10 but the between group difference was not statistically significant.
在第 10 周时，LAC 组的平均得分明显提高，但组间差异无统计学意义。
Treatment was well tolerated and the number (42% in the placebo group and in the LAC group) and severity of adverse events were similar in the two groups of patients. They were associated to treatment discontinuation for 3 and 5 subjects of the placebo and LAC group, respectively.
两组患者对治疗的耐受性良好，不良反应的数量（安慰剂组为42%，LAC组为 ）和严重程度相似。安慰剂组和LAC组分别有3名和5名患者因不良反应而停止治疗。

Discussion

In this randomized, double blind, 10 week trial in subjects with ACR-defined primary FMS, LAC treatment had significantly greater efficacy than placebo on the primary end-point of the study (total myalgic score) but also on several other outcome measures. The baseline assessment demonstrated that this study population was similar to those in other studies of patients with FMS (6). The efficacy of LAC on pain was consistent for all adopted assessment tools: total myalgic score, number of positive tender points, VAS for musculo-skeletal pain, SF-36 domain for bodily pain. Improvements in general heath status and mental health were also observed. These improvements were likely linked to improvement in pain, since there appears to be a significant correlation between changes in pain and in general health perception in the two groups individually and in the study population as a whole (data not shown).
在这项针对 ACR 定义的原发性 FMS 受试者进行的为期 10 周的随机双盲试验中，在研究的主要终点（肌痛总分）以及其他几项结果指标上，LAC 治疗的疗效明显优于安慰剂。基线评估结果表明，这项研究的受试者与其他 FMS 患者研究的受试者相似（6）。在所有采用的评估工具中，LAC 对疼痛的疗效是一致的：肌痛总分、阳性触痛点数量、肌肉骨骼疼痛 VAS、SF-36 身体疼痛域。总体健康状况和心理健康也有所改善。这些改善很可能与疼痛的改善有关，因为在两组个体和整个研究人群中，疼痛和一般健康感知的变化之间似乎存在着显著的相关性（数据未显示）。
Self-evaluated depression also improved, and this finding is in line with some preliminary reports on the efficacy of LAC on primary depression (17-22). However, it should be pointed out that depression in our cohort was moderate and therefore the Hamilton score could not be properly used for assessing improvements. It remains to be established whether these minor improvements in depression were the cause or the consequence of the pain benefits. All anti-depressant agents, including to a certain extent also LAC, seem to provide symptomatic relief in patients with FMS, before or inde-
自我评估的抑郁情况也有所改善，这一发现与一些关于 LAC 对原发性抑郁疗效的初步报告（17-22）相一致。然而，应该指出的是，我们队列中的抑郁程度为中度，因此无法正确使用汉密尔顿评分来评估抑郁的改善情况。抑郁症的轻微改善是疼痛获益的原因还是结果，还有待确定。所有抗抑郁药物，在一定程度上也包括 LAC，似乎都能缓解 FMS 患者的症状，无论是在服药前还是服药后。
Fig. 3. Changes in VAS score for subjective symptoms from baseline to the end of the treatment. *
图 3.主观症状 VAS 评分从基线到治疗结束的变化。*
Fig. 4. Changes in the main domains of the SF36 questionnaire from baseline to the end of the treatment.
图 4.从基线到治疗结束期间，SF36 问卷主要领域的变化情况。
pendent of their effect on depression. This might suggest a pain-modulating effect of these compounds on peripheral or central nervous system, not dependent on the modulation of mood (27-29).
与它们对抑郁的影响无关。这可能表明这些化合物对外周或中枢神经系统具有疼痛调节作用，而不依赖于对情绪的调节（27-29）。
The changes in pain and general health we observed are comparable to those recently reported in two randomized clinical trials of duloxetine and pregabalin, even though the placebo effect in our cohort was somewhat greater, with significant improvements for most efficacy assessment items . This
我们观察到的疼痛和一般健康状况的变化与最近在度洛西汀和普瑞巴林的两项随机临床试验中报告的变化相当，尽管我们队列中的安慰剂效应更大一些，大多数疗效评估项目 都有显著改善。这
might be attributed to the complexity of the dosing regimen that included an intra-muscular injection, perceived in the Italian population as a "strong" treatment approach. Anyhow, our results emphasize the need for accurate double blind randomized clinical trials when evaluating any pharmacologic treatment of FMS. The placebo effect may possibly explain the delay in the longitudinal pain response to LAC. The difference between the two groups becomes statistically significant only when, as expected, the placebo effect waned after the first 4-6 weeks of observation.
这可能是由于用药方案的复杂性，其中包括肌肉注射，而意大利人认为肌肉注射是一种 "强效 "治疗方法。无论如何，我们的研究结果表明，在评估任何 FMS 药物治疗时，都需要进行准确的双盲随机临床试验。安慰剂效应可能解释了对 LAC 的纵向疼痛反应的延迟。只有当安慰剂效应在头 4-6 周的观察后减弱时，两组之间的差异才会如预期的那样具有统计学意义。
The delayed response may also be related to the mechanism of action of LAC. LAC is a physiological compound synthesized in the mitochondria. When given at an apparent cholinergic effect associated with an inhibitory competitive effect on the GABA re-ceptor complex, thereby explaining the anti-depressant activity of LAC (17-22). In addition LAC facilitates mitochondrial beta-oxidation of fatty acids, through the Krebs' cycle with a potential beneficial effect on both sensitive and motor peripheral nerves (3133). These latter metabolic effects are likely to be fully expressed only with an extended time lag. LAC may also have a role in reducing the disturbances of muscle blood flow described in FM patients, the hypoxic stress of tissues, especially at the onset of exercise, and the oxidative disorder recently reported in primary FMS (34-38).
延迟反应也可能与 LAC 的作用机制有关。LAC 是一种在线粒体中合成的生理化合物。当给予 LAC 时，其明显的胆碱能效应与 GABA 再受体复合体的抑制竞争效应有关，从而解释了 LAC 的抗抑郁活性（17-22）。此外，LAC 还能通过克雷布斯循环促进线粒体脂肪酸的β-氧化，从而对敏感神经和运动性末梢神经产生潜在的有益影响（3133）。后一种新陈代谢效应可能要经过较长的时间滞后才能充分表现出来。LAC 还可能在减少 FM 患者肌肉血流紊乱、组织缺氧压力（尤其是在运动开始时）以及最近报道的原发性 FMS 氧化紊乱方面发挥作用（34-38）。
The analysis of our results as well as those recently reported with duloxetine and pregabalin, may provide some insights on the pathophysiology of FMS . In these trials the beneficial effect on pain was not associated with improvement in fatigue or anxiety indicating that some of the underlining psychological and/or metabolic ab-normalities remain unsolved.
对我们的研究结果以及最近报道的度洛西汀和普瑞巴林的研究结果进行分析，可能会对FMS的病理生理学 提供一些启示。在这些试验中，对疼痛的有益影响与疲劳或焦虑的改善无关，这表明一些基本的心理和/或代谢异常问题仍未得到解决。
Recent studies demonstrate that LAC treatment improves fatigue in patients with chronic fatigue syndrome and in multiple sclerosis, and is efficacious in alleviating symptoms, particularly pain, and improves nerve fiber regeneration and vibration perception in patients with established diabetic neuropathy (39-41).
最近的研究表明，LAC 治疗可改善慢性疲劳综合症患者和多发性硬化症患者的疲劳状况，并能有效缓解症状，尤其是疼痛，还能改善糖尿病神经病变患者的神经纤维再生和振动感知（39-41）。
Although this experience deserves further studies, these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.
尽管这一经验值得进一步研究，但这些结果表明，LAC 可能对 FMS 患者有益，可以改善这些患者的疼痛以及全身和心理健康。

Acknowledgments 致谢

Prof. Alessandro Ciocci (Roma), Prof. Filippo Roberto Marcolongo (Siena), Prof. Pasquale Oriente (Napoli), Prof. Giuseppe Perpignano (Cagliari) also contributed to data collection at their centers. Dimensione Ricerca S.p.A. (Rome) was in charge of data collection and statistical analysis.
Alessandro Ciocci 教授（罗马）、Filippo Roberto Marcolongo 教授（锡耶纳）、Pasquale Oriente 教授（那不勒斯）、Giuseppe Perpignano 教授（卡利亚里）也在各自的研究中心参与了数据收集工作。Dimensione Ricerca S.p.A.（罗马）负责数据收集和统计分析。

References

  1. WOLFE F, SMYTHE HA, YUNUS MB et al.: The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 1990; 33: 16072 .
    WOLFE F、SMYTHE HA、YUNUS MB 等人：美国风湿病学会 1990 年纤维肌痛分类标准。多中心标准委员会报告。Arthritis Rheum 1990; 33: 16072 .
  2. WOLFE F, ROSS K, ANDERSON J, RUSSELL IJ, HEBERT L: The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum 1995; 38: 19-28.
    WOLFE F、ROSS K、ANDERSON J、RUSSELL IJ、HEBERT L：纤维肌痛在普通人群中的患病率和特征。Arthritis Rheum 1995; 38: 19-28.
  3. BENNETT RM: The rational management of fibromyalgia patients. Rheum Dis Clin North Am 2002; 28: 181-99.
    BENNETT RM：纤维肌痛患者的合理管理。Rheum Dis Clin North Am 2002; 28: 181-99.
  4. CLAUW DJ, CROFFORD LJ: Chronic widespread pain and fibromyalgia: what we know, and what we need to know. Best Pract Res Clin Rheumatol 2003; 17: 685-701.
    Clauw DJ, crofford LJ：慢性广泛性疼痛与纤维肌痛：我们知道什么，我们需要知道什么。Best Pract Res Clin Rheumatol 2003; 17: 685-701.
  5. BARKHUIZEN A: Rational and targeted pharmacologic treatment of fibromyalgia. Rheum Dis Clin North Am 2002; 28: 261-90.
    BARKHUIZEN A：纤维肌痛的合理和针对性药物治疗。Rheum Dis Clin North Am 2002; 28: 261-90.
  6. MEASE P: Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol 2005; 32 (Suppl. 75): 6-21.
    MEASE P：纤维肌痛综合征：临床表现、发病机制、结果测量和治疗回顾。J Rheumatol 2005; 32 (Suppl. 75)：6-21.
  7. BUSCH A, SCHACHTER C, PELOSO P, BOMBARDIER C: Exercise for treating fibromyalgia syndrome. Cochrane Database Syst Rev 2002; CD003786
    BUSCH A、SCHACHTER C、PELOSO P、BOMBARDIER C：治疗纤维肌痛综合征的运动。Cochrane Database Syst Rev 2002; CD003786
  8. BURCKHARDT CS, MANNERKORPI K, HEDENBERG L, BJELLE A: A randomized, controlled clinical trial of education and physical training for women with fibromyalgia. J Rheumatol 1994; 21: 714-20.
    BURCKHARDT CS、MANNERKORPI K、HEDENBERG L、BJELLE A：针对纤维肌痛妇女的教育和体育训练随机对照临床试验。J Rheumatol 1994; 21: 714-20。
  9. WILLIAMS DA: Psychological and behavioural therapies in fibromyalgia and related syndromes. Best Pract Res Clin Rheumatol 2003; 17: 649-65.
    WILLIAMS DA：纤维肌痛及相关综合征的心理和行为疗法。Best Pract Res Clin Rheumatol 2003; 17: 649-65。
  10. EISINGER J: Metabolic abnormalities in fibromyalgia. Clin Bull of Myofascial Therapy 1998; Vol 3: 3-21.
    EISINGER J：纤维肌痛的代谢异常。肌筋膜治疗临床公牛》，1998 年；第 3 卷：3-21。
  11. BENGTSSON A, HENRIKSSON KG, LARSSON : Muscle biopsy in primary fibromyalgia: light-microscopical and histochemical findings. Scand J Rheumatol 1986; 15:1-6.
    BENGTSSON A, HENRIKSSON KG, LARSSON ：原发性纤维肌痛的肌肉活检：光学显微镜和组织化学检查结果。Scand J Rheumatol 1986; 15:1-6.
  12. BENGTSSON A, HENRIKSSON KG, LARSSON J: Reduced high energy phosphate levels in the painful muscles of patients with primary fibromyalgia. Arthritis Rheum 1986; 7: 81721.
    BENGTSSON A、HENRIKSSON KG、LARSSON J：原发性纤维肌痛患者疼痛肌肉中的高能磷酸水平降低。Arthritis Rheum 1986; 7: 81721.
  13. BENGTSSON A, CEDERBLAD G, LARSSON : Carnitine levels in painful muscles of patients with fibromyalgia. Clin Exp Rheumatol 1990; 8: 197-200.
    BENGTSSON A, CEDERBLAD G, LARSSON ：纤维肌痛患者疼痛肌肉中的肉碱水平。Clin Exp Rheumatol 1990; 8: 197-200.
  14. SPAETH M, STRATZ TH: Carnitine deficiency and fibromyalgia. Arthritis Rheum 1999, 42: 479 .
    SPAETH M，STRATZ TH：肉碱缺乏与纤维肌痛。Arthritis Rheum 1999, 42: 479 .
  15. EISINGER J, ZAKARIAN H, POULY E et al.: Dosage de la carnitine plasmatique au cours
    EISINGER J、ZAKARIAN H、POULY E 等人：血浆中肉碱的测定。
    des fibromyalgies. Lyon Mediter Med 1997; 33: 2369-72.
    des fibromyalgies.Lyon Mediter Med 1997; 33: 2369-72.
  16. DUBELAAR ML, LUCAS CMHB, HULSMANN F et al.: Acute effect of L-carnitine on skeletal muscle force tests in dogs. Am J Physiol 1991; 260:189-93
    DUBELAAR ML、LUCAS CMHB、HULSMANN F 等人：左旋肉碱对狗骨骼肌力量测试的急性影响Am J Physiol 1991; 260:189-93
  17. VILLARDITA C, SMIRNI P, LE PIRA F et al.: Lacetyl-carnitina in depressed elderly patients. Eur Rev Med Pharmacol Sci 1984; 6: 34144.
    VILLARDITA C、SMIRNI P、LE PIRA F 等人：Lacetyl-carnitina 在老年抑郁症患者中的应用。Eur Rev Med Pharmacol Sci 1984; 6: 34144.
  18. TEMPESTA E, CASELLA L, PIZZONGELLI C et al.: L-acetyl-carnitina in depressed elderly subjects. A cross-over study vs placebo. Drugs Exp Clin Res 1987; 13: 417-23.
    TEMPESTA E, CASELLA L, PIZZONGELLI C et al：L-acetyl-carnitina 在老年抑郁症患者中的应用。与安慰剂的交叉研究。药物临床研究》，1987 年；13：417-23。
  19. GARZYA G, CORALLO D, FIORE A et al.: Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res 1990; 16: 101-6.
    GARZYA G、CORALLO D、FIORE A 等人：评估左旋乙酰肉碱对老年抑郁症患者的影响》。药物临床研究》，1990 年；16：101-6。
  20. BELLA R, BIONDI R, RAFFAELE R, PENNISI G: Effect of acetyl-carnitine on geriatric patients suffering from dysthymic disorders. Int J Clin Pharm Res 1990; 10: 355-36.
    BELLA R、BIONDI R、RAFFAELE R、PENNISI G：乙酰肉碱对癔症老年患者的影响。Int J Clin Pharm Res 1990; 10: 355-36.
  21. FULGENTE T, ONOFRI M, DEL RE ML et al.: Laevo-acetylcarnitine (Nicetile) treatment of senile depression. Clin Trials J 1990; 27: 155-63.
    FULGENTE T、ONOFRI M、DEL RE ML 等人：来乙酰肉碱（Nicetile）治疗老年抑郁症。临床试验 J 1990; 27: 155-63.
  22. GECELE M, FRANCESETTI G, MELUZZI A: Acetyl-L-carnitine in aged subjects with major depression: Clinical efficacy and effects on the circadian rhythm of Cortisol. Dementia 1991; 2: 333-7.
    GECELE M、FRANCESETTI G、MELUZZI A：乙酰基-L-肉碱对老年重度抑郁症患者的临床疗效及对皮质醇昼夜节律的影响：临床疗效及对皮质醇昼夜节律的影响。痴呆 1991; 2: 333-7。
  23. FISCHER AA: Pressure threshold meter: its use for quantification of tender spots. Arch Phys Med Rehabil 1986; 67: 836-8.
    FISCHER AA：压力阈值测量仪：用于对压痛点进行量化。Arch Phys Med Rehabilitation 1986; 67: 836-8.
  24. WARE JE JR, SHERBOURNE CD: The MOS 36-item Short-form Health Survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473-83.
    ware je jr, Sherbourne CD：MOS 36 项短式健康调查（SF-36）。I. 概念框架和项目选择。Med Care 1992; 30: 473-83.
  25. HAMILTON M: A rating scale for depression. Neurol Neurosurg Psychiatry 1960; 23: 56-62.
    HAMILTON M: A rating scale for depression. Neurol Neurosurg Psychiatry 1960; 23: 56-62.
  26. FARIES D, HERRERA J, RAYAMAJHI J, DEBROTA D, DEMITRACK M, POTTER WZ: The responsiveness of the Hamilton Depression Rating Scale. J Psychiatric Res 2000; 34: 310 .
    FARIES D, HERRERA J, RAYAMAJHI J, DEBROTA D, DEMITRACK M, POTTER WZ：汉密尔顿抑郁评定量表的反应性。J Psychiatric Res 2000; 34: 310 .
  27. ARNOLD LM, KECK PE JR, WELGE JA: Antidepressant treatment of fibromyalgia. A meta-analysis and review. Psychosomatics 2000; 41: 104-13.
    ARNOLD LM、KECK PE JR、WELGE JA：纤维肌痛的抗抑郁治疗。荟萃分析与回顾。Psychosomatics 2000; 41: 104-13.
  28. ARNOLD LM, LU Y, CROFFORD LJ et al.: Double-blind, multicenter trial comparing duloxetine with placebo in the treatment of fibromyalgia patients with or without major depressive disorder. Arthritis Rheum 2004; 50: .
    ARNOLD LM、LU Y、CROFFORD LJ 等人：在治疗伴有或不伴有重度抑郁障碍的纤维肌痛患者时比较度洛西汀与安慰剂的双盲多中心试验。Arthritis Rheum 2004; 50: .
  29. O'MALLEY PG, BALDEN E, TOMKINS G, SANTORO J, KROENKE K, JACKSON JL: Treatment of fibromyalgia with anti-depressants: a meta-analysis. J Gen Intern Med 2000; 15: 659-66.
    O'MALLEY PG、BALDEN E、TOMKINS G、SANTORO J、KROENKE K、JACKSON JL：用抗抑郁药治疗纤维肌痛：荟萃分析。J Gen Intern Med 2000; 15: 659-66。
  30. CROFFORD LJ, ROWBOTHAM MC, MEASE PJ et al.: Pregabalin for the treatment of fibromyalgia syndrome: Results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum 2005; 52: 1264-73.
    CROFFORD LJ, ROWBOTHAM MC, MEASE PJ et al：普瑞巴林治疗纤维肌痛综合征：随机、双盲、安慰剂对照试验结果。Arthritis Rheum 2005; 52: 1264-73.
  31. BENNET RM: The contribution of muscle to the generation of fibromyalgia symptomatology. J Musculoskeletal Pain 1996; 4: 35-49.
    BENNET RM：肌肉对纤维肌痛症状产生的贡献。J Musculoskeletal Pain 1996; 4: 35-49.
  32. FALCHETTO S, KATO G, PROVINI L: The action of carnitines on cortical neurons. Can J Physiol Pharmacol 1971; 49: 1-7.
    FALCHETTO S、KATO G、PROVINI L：肉毒碱对大脑皮层神经元的作用。Can J Physiol Pharmacol 1971; 49: 1-7.
  33. FANELLI O: Carnitine and acetyl-carnitine, natural substances endowed with interesting pharmacologica properties. Life Sci 1978; 23: 2563-70.
    FANELLI O：肉碱和乙酰肉碱，具有有趣药理特性的天然物质。生命科学，1978 年；23：2563-70。
  34. KRAEMER WJ, VOLEK JS, SPIERING BA,
    KRAEMER WJ, VOLEK JS, SPIERING BA、
    VINGREN JL: L-carnitine supplementation: a new paradigm for its role in exercise. Monatshefte fur Chemie 2005; 136: 1383-90.
    VINGREN JL：补充左旋肉碱：其在运动中作用的新范例。Monatshefte fur Chemie 2005; 136: 1383-90.
  35. ELVIN A, SIOSTEEN AK, NILSSON A, KOSEK E: Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: a contrast media enhanced colour doppler study. Eur J Pain 2006; 10: 137-44.
    ELVIN A、SIOSTEEN AK、NILSSON A、KOSEK E：纤维肌痛患者在进行标准化肌肉锻炼时肌肉血流量减少：造影剂增强彩色多普勒研究。Eur J Pain 2006; 10: 137-44.
  36. ROBERTS PA, LOXHAM SJG, POUCHER SM, CONSTANTIN-TEODOSIU D, GREENHAFF PL: Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle. Am J Physiol Endocrinol Metab 2005; 288: E327-E334.
    ROBERTS PA、LOXHAM SJG、POUCHER SM、CONSTANTIN-TEODOSIU D、GREENHAFF PL：缺血犬骨骼肌收缩开始时乙酰-CoA 的供应和乙酰基缺失。Am J Physiol Endocrinol Metab 2005; 288: E327-E334.
  37. BAGIS S, TAMER L, SAHIN G et al.: Free radicals and antioxidants in primary fibromyalgia: an oxidative stress disorder? Rheumatol Int 2005; 25: 188-90.
    BAGIS S、TAMER L、SAHIN G 等人：原发性纤维肌痛中的自由基和抗氧化剂：氧化应激紊乱？Rheumatol Int 2005; 25: 188-90。
  38. OZGOCMEN S, OZYURT H, SOGUT S, AKYOL O: Current concepts in the pathophysiology of fibromyalgia: the potential role of oxidative stress and nitric oxide. Rheumatol Int 2005: 1-13.
    OZGOCMEN S、OZYURT H、SOGUT S、AKYOL O：纤维肌痛病理生理学的当前概念：氧化应激和一氧化氮的潜在作用。Rheumatol Int 2005: 1-13.
  39. PLIOPLYS AV, PLIOPLYS S: Amantadine and L-carnitine treatment of chronic fatgue syndrome. Neuropsychobiology 1997; 35: 1623 .
    PLIOPLYS AV，PLIOPLYS S：金刚烷胺和左旋肉碱治疗慢性疲劳综合征。神经心理生物学 1997; 35: 1623 。
  40. TOMASSINI V, POZZILLI C, ONESTI E et al.: Comparison of the effects of Acetyl-1-Carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Neurol Sci 2004; 218: 103-8.
    TOMASSINI V、POZZILLI C、ONESTI E 等人：乙酰-1-肉碱和金刚烷胺治疗多发性硬化症患者疲劳的效果比较：随机、双盲、交叉试验的结果。 Neurol Sci 2004; 218: 103-8.
  41. SIMA AAF, CALVANI M, MEHRA M, AMATO A: Acetyl-L-Carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy. Diabetes Care 2005; 28: 89-94.
    SIMA AAF、CALVANI M、MEHRA M、AMATO A：乙酰-L-肉碱能改善慢性糖尿病神经病变患者的疼痛、神经再生和振动感知。糖尿病护理》，2005 年；28：89-94。