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【有奖摘要翻译】第十三期: Pregabalin AND pain

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第十三期主题:Pregabalin AND pain

当前在神经痛治疗中,普瑞巴林(Pregabalin)日渐成为研究热点,其治疗带状疱疹后神经痛和糖尿病神经痛已逐渐得到大家的认可,有关该药的应用和机制的研究很多,本期精选有关的相关摘要14篇,希望通过此大家对该药有一进一步的理解。


论文摘要目录:

1: Clin Ther. 2007 Jan;29(1):26-48.
Pregabalin: A novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. [kentlee22战友已申领]

2: Neurosci Lett. 2007 Mar 2;
[(3)H] pregabalin binding is increased in ipsilateral dorsal horn following chronic constriction injury. [rena_liu战友已申领]

3: Yonsei Med J. 2007 Feb 28;48(1):41-7.
Antiallodynic effect of pregabalin in rat models of sympathetically maintained and sympathetic independent neuropathic pain. [rena_liu战友已申领]

4: J Pain. 2007 Feb 8;
Pregabalin Reduces Muscle and Cutaneous Hyperalgesia in Two Models of Chronic Muscle Pain in Rats. [llc168战友已申领]

5: Br J Anaesth. 2007 Feb;98(2):246-54.
Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. [kentlee22战友已申领]

6: Pain Pract. 2005 Dec;5(4):327-40.
Postherpetic neuralgia: the never-ending challenge. [printhome战友已申领]

7: Neurology. 2006 Nov 28; 67(10):1792-800.
Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. [printhome战友已申领]

8: Epilepsy Res. 2007 Feb;73(2):137-50. Epub 2006 Nov 28.
Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery. [hujinyu1战友已申领]

9: Eur J Pharmacol. 2006 Dec 28;553(1-3):82-8. Epub 2006 Sep 23.
Pregabalin action at a model synapse: binding to presynaptic calcium channel alpha2-delta subunit reduces neurotransmission in mice. [yuanliyong战友已申领]

10: Pain Res Manag. 2006 Summer;11 Suppl A:16A-29A.
Gabapentin and pregabalin for the treatment of neuropathic pain: A review of laboratory and clinical evidence. [hujinyu1战友已申领]

11: Neurologia. 2006 Mar;21(2):96-103.
[Pregabalin. A new treatment for neuropathic pain [killerlsh2000战友已申领]

12: Drugs. 2005;65(1):111-8; discussion 119-20.
Pregabalin: in the treatment of postherpetic neuralgia. [killerlsh2000战友已申领]

13: Neurology. 2004 Dec 14;63 (11):2104-10.
Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial. [huangyixiao98战友已申领]

14: Pain. 2004 Aug;110(3):628-38.
Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial. [huangyixiao98战友已申领]

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Pregabalin AND pain.doc (77.5k)
版主您好,我认领第二篇和第三篇摘要。
认领11、12(综述)。
认领6 7

6: Pain Pract. 2005 Dec;5(4):327-40.

Postherpetic neuralgia: the never-ending challenge.

Niv D, Maltsman-Tseikhin A.

Center for Pain Medicine, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Postherpetic neuralgia (PHN) is defined as pain that persists 1 to 3 months following the rash of herpes zoster (HZ). PHN affects about 50% of patients over 60 years of age and 15% of all HZ patients. Patients with PHN may experience two types of pain: a steady, aching, boring pain and a paroxysmal lancinating pain, usually exacerbated by contact with the involved skin. Herpes zoster is initially a clinical diagnosis, based on the observation of a typical dermatomal distribution of rash and radicular pain. HZ is pathologically characterized by inflammatory necrosis of dorsal root ganglia, occasionally associated with evidence of neuritis, leptomeningitis, and segmental unilateral degeneration of related motor and sensory roots. Although acyclovir has been used successfully as standard therapy for varicella zoster virus (VZV) infection in the past decade, resistant strains of VZV are often recognized in immunocompromised patients. Therapy with acyclovir and the use of corticosteroids have been reported to prevent PHN in up to 60% of HZ patients. Management of chronic pain in PHN is more problematic. The only therapy proven effective for PHN in controlled study is the use of tricyclic antidepressants, including amitriptyline and desipramine. There is good evidence of efficacy from randomized trials that gabapentin and pregabalin (new anticonvulsant drugs) are of benefit in the reduction of pain from PHN. As alternative therapies, topical agents such as capsaicin, lidocaine or opioid analgesic treatment may give satisfactory results. Interventions with low risk, such as transcutaneous electrical nerve stimulation (TENS), are appropriate. Evidence is scant for the value of surgical and procedural interventions in general, although there are numerous, small studies supporting the use of specific interventions such as nerve blocks, neurosurgical procedures, and neuroaugmentation. Although antiviral agents are appropriate for acute HZ, and the use of neural blockade and sympathetic blockade may be helpful in reducing pain in selected patients with HZ, there is little evidence that these interventions will reduce the likelihood of developing PHN. Postherpetic neuralgia remains a difficult pain problem. This review describes the epidemiology and pathophysiology of PHN and discusses proposed mechanisms of pain generation with emphasis on the various pharmacological treatments and invasive modalities currently available.

6、带状疱疹后神经痛:无尽的挑战

译者:printhome
带状疱疹后神经痛 (PHN)是指继发于带状疱疹(HZ),持续1-3月的疼痛。PHN在60岁以上HZ患者中发生率为50%,在所有HZ患者中发生率为15%。PHN患者疼痛主要有两种类型:持续的钝痛和阵发性锐痛,当涉及到皮肤时,疼痛常加剧。
HZ最初是根据典型的皮肤疱疹和神经根性疼痛的典型分布,进行临床诊断。 HZ病理表现为背根神经节的炎性坏死,偶伴有神经炎、软脑脊膜炎、节段性单侧相关运动和感觉神经根的变性。近十年来,尽管阿昔洛韦药疗是水痘-疱疹病毒(VZV)感染的最成功的标准治疗方法,在免疫低下患者中仍经常发现有VAV的耐药株。
阿昔洛韦与皮质激素联合应用可使60%HZ患者免于PHN,PHN慢性疼痛的治疗目前仍较困难。目前,控制PHN的对照研究,仅有三环类抗抑郁药被证实有效,如阿米替林、地昔帕明。有随机试验表明,加巴喷丁与抗惊厥新药普加巴林可有效控制PHN。辣椒碱、利多卡因及阿片类镇痛药,作为替代疗法均有较好的止痛效果。低风险的操作如经皮电刺激神经疗法(TENS)也可控制PHN。PHN的外科治疗目前尚为证实有效,尽管目前有大量小型研究表明,特异性操作如神经阻滞、神经外科手术可控制PHN。抗病毒药物适用于急性HZ,神经阻滞及交感神经阻滞有助于减缓部分HZ患者疼痛,目前尚无证据表明上述治疗能降低HZ向PHN的进展。
带状疱疹后神经痛目前依然是临床的一大难题。本文综述了PHN的流行病学和病理生理机制,探讨疼痛发生的可能机制,并重点对各种药物治疗及有创治疗进行了深入介绍.
7、Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial.

Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK.

Pain Management and Research Institute, University of Sydney, Royal North Shore Hospital, Sydney, NSW, 2065, Australia. phils@med.usyd.edu.au

OBJECTIVE: To evaluate pregabalin in central neuropathic pain associated with spinal cord injury. METHODS: A 12-week, multicenter study of patients randomized to either flexible-dose pregabalin 150 to 600 mg/day (n = 70) or placebo (n = 67), administered BID. Patients were allowed to remain on existing, stable pain therapy. The primary efficacy variable was the endpoint mean pain score, derived from patients' last 7 days daily pain diary entries. Key secondary endpoints included pain responder rates, the SF-MPQ, sleep interference, mood, and the patient global measure of change. RESULTS: The mean baseline pain score was 6.54 in the pregabalin group and 6.73 in the placebo group. The mean endpoint pain score was lower in the pregabalin group (4.62) than the placebo group (6.27; p < 0.001), with efficacy observed as early as week 1 and maintained for the duration of the study. The average pregabalin dose after the 3-week stabilization phase was 460 mg/day. Pregabalin was significantly superior to placebo in endpoint assessments on the SF-MPQ. The > or =30% and > or =50% pain responder rates were higher with pregabalin than placebo (p < 0.05). Pregabalin was associated with improvements in disturbed sleep (p < 0.001) and anxiety (p < 0.05), and more patients reported global improvement at endpoint in the pregabalin group (p < 0.001). Mild or moderate, typically transient, somnolence and dizziness were the most common adverse events. CONCLUSIONS: Pregabalin 150 to 600 mg/day was effective in relieving central neuropathic pain, improving sleep, anxiety, and overall patient status in patients with spinal cord injury.

7、普瑞巴林治疗伴有脊髓损伤的中枢性神经疼痛的安慰剂对照试验

译者:printhome
目的:评价普瑞巴林用于伴随有脊髓损伤的中枢性神经疼痛的治疗效果。方法:在一项为期12周多中心试验中,将患者随机分为普瑞巴林组(n=70)与安慰剂组(n=67),其中普瑞巴林组药物剂量在150-600mg/天,口服,2/日。允许患者继续原有镇痛治疗。本研究首要评估指标为根据患者疼痛日记,评估研究终末点平均疼痛评分。次要评估指标包括药物起效率、SF-MPQ、睡眠、情绪、全身状况。 结果:普瑞巴林组平均基础疼痛评分6.54,对照组为6.73。从用药第一周至本研究结束,普瑞巴林组终点平均疼痛评分为4.62,低于对照组6.27(p<0.001)。在第3周药量稳定后,普瑞巴林平均用药量为460mg/天。按照SF-MPQ进行终末评估,普瑞巴林显著优于安慰剂对照组。普瑞巴林组药物起效率大于或等于30%及50% 者显著高于对照组(p < 0.05)(p < 0.05)。普瑞巴林同时可改善睡眠紊乱(p<0.001)及焦虑(p < 0.05), 大多数患者反映,全身一般状况好转(p < 0.001)。普瑞巴林的最常见副反应为轻度或短暂嗜睡或头晕。结论:普瑞巴林150-600mg/天可有效减轻脊髓损伤患者中枢性神经疼痛,促进睡眠、减缓焦虑,改善全身状况。
11: Neurologia. 2006 Mar;21(2):96-103.

[Pregabalin. A new treatment for neuropathic pain]

Lopez-Trigo J, Sancho Rieger J.

Servicio de Neurologia, Consorcio Hospital General Universitario, Valencia. neurofisiologia_hgva@es

Neuropathic pain is a condition affecting a significant proportion of the world's population. Many therapeutic drugs have been used. They achieve less than satisfactory results and are associated to common side effects that affect the daily life of patients. Pregabalin is a new drug that has been shown to be effective for treating partial epilepsy and peripheral neuropathic pain in clinical trials. It is a structural, but not functional, analogue of GABA. It acts as a ligand of the alpha2-delta subunit, a protein associated to the voltage-dependent calcium channels. Modulation of these channels decreases calcium entry into nerve endings, resulting in a decreased release of several excitatory neurotransmitters. Pregabalin had a linear pharmacokinetics with little variability between the different subjects. It does not bind to plasma proteins, has no liver metabolism, and is excreted trough the kidneys. Few interactions with other drugs may be expected based on these characteristics. In clinical trials, pregabalin has been shown to be effective in postherpetic neuralgia and painful diabetic neuropathy at doses ranging from 150-600 mg/day. The analgesic effects of pregabalin occur in the first few days of treatment and are sustained over time. Side effects are few; most are transient and well-tolerated by patients, and the treatment discontinuation rate is minimal.
普瑞巴林:神经病理性疼痛的新治疗
神经病理性疼痛困扰着全球相当比例人群受。尽管多种药物用于治疗,但都难以取得满意的效果,且伴有影响病人日常生活的常见负作用。普瑞巴林是一种新药,临床试验显示,它能有效治疗局灶性癫痫和外周神经性疼痛。普瑞巴林结构类似GABA,但功能不同,其作用机制是作为配体与α2δ亚单位结合,后者与电压依赖性钙通道有关,通过调节钙通道减少钙离子进入神经末梢,使几种兴奋性神经递质释放减少。体内代谢过程呈线性,几无个体差异。在血中与不与血浆蛋白结合,也无肝代谢,通过肾脏排泄。因此可以推测,普瑞巴林与其它药物几无相互作用。临床试验中,普瑞巴林150-600 mg/d可有效治疗带状疱疹后神经痛和糖尿病神经痛,镇痛作用出现早(1-数天内),停药后仍维持一定时间。几无副作用,且多数时间短暂、病人可以耐受,少有因副作用停药者。

12: Drugs. 2005;65(1):111-8; discussion 119-20.

Pregabalin: in the treatment of postherpetic neuralgia.

Frampton JE, Foster RH.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Pregabalin, the pharmacologically active S-enantiomer of 3-aminomethyl-5-methyl-hexanoic acid, has a similar pharmacological profile to that of its developmental predecessor gabapentin, but showed greater analgesic activity in rodent models of neuropathic pain. The exact mechanism of action of pregabalin is unclear, although it may reduce excitatory neurotransmitter release by binding to the alpha2-delta protein subunit of voltage-gated calcium channels. Oral pregabalin 150-600 mg/day, administered twice or three times daily, was superior to placebo in relieving pain and improving pain-related sleep interference in three randomised, double-blind, placebo-controlled, multicentre studies of 8-13 weeks' duration in a total of 776 evaluable patients with postherpetic neuralgia (PHN). Weekly mean pain scores (primary endpoint; assessed in all three studies) and weekly mean sleep interference scores (assessed in two studies) were significantly improved at 1 week. In two studies, significant improvements in daily mean pain scores were apparent on the first or second day of treatment with pregabalin administered three times daily. Pregabalin was generally well tolerated when force-titrated over 1 week to fixed dosages (maximum 600 mg/day) in clinical trials that enrolled most elderly PHN patients. Dizziness, somnolence and peripheral oedema of mild-to-moderate intensity were the most common adverse events. Publication Types:

PMID: 15610058 [PubMed - indexed for MEDLINE]
普瑞巴林治疗带状疱疹后神经痛
普瑞巴林为3-氨甲基-5-甲基-乙酸S型映构体,药理活性与其前体加巴喷丁类似,但在神经性疼痛的啮齿动物模型中显示出较后者更好的镇痛效果。它通过与电压依赖性钙通道中的α2δ亚单位结合,可降低兴奋性神经递质的释放,但确切作用机制仍不清楚。在三个历时8-13w、总有效样本量776例的带状疱疹随机、双盲、安慰剂对照的多中心研究中,普瑞巴林150-600 mg/d、每日2-3次口服,在缓解疼痛和改善疼痛相关睡眠障碍方面优于对照组,周平均疼痛评分(3个研究中的第一评价终点)和平均睡眠障碍评分(2个研究)在治疗一周后明显改善,在其中2个研究中,病人接受普瑞巴林每日3次口服治疗,日平均疼痛评分在治疗第一或第二天即明显改善。在观察对象多为老年带状疱疹后神经痛的临床试验中,一周左右时间将普瑞巴林剂量逐渐调定至固定剂量(最大剂量600mg/d),病人普遍耐受良好。最常见不良反应为眩晕、嗜睡、和轻到中度的外周水肿。
我认领第8,10篇,择日张贴,谢谢!
13 普瑞巴林缓解糖尿病神经痛症状:一项随机对照试验

目的:普瑞巴林,一种α2δ配体,具有镇痛、抗焦虑、抗惊厥活性,已经过评估可用于治疗神经病理性疼痛。作者研究了在患有糖尿病周围神经痛(DPN)的患者中,普瑞巴林(75, 300, 600 mg/天)与安慰剂相比,其疗效和耐受性。
方法:有1-5年DPN史,且周平均疼痛评分> 或 =4(11分的数字疼痛评分量表)的患者被纳入此项为期5周、双盲、多中心、安慰剂对照研究。患者(n = 338)被随机分为接受三种普瑞巴林剂量之一或者安慰剂组,每天三次。普瑞巴林从小剂量开始逐步增加剂量,六天后增加到600mg/天。。
结果:300和600mg普瑞巴林组患者与安慰剂组比,研究终点时平均疼痛评分(主要的疗效评估指标)有改善(p = 0.0001)。周疼痛评分,睡眠障碍评分,患者对变化的总体印象(patient global impression of change),临床变化总体印象(clinical global impression of change),SF-McGill疼痛问卷(SF-McGill Pain Questionnaire),和多域SF-36健康调查(multiple domains of the SF-36 Health Survey)也有改善。早在第一周即可见到疼痛和睡眠改善,并且在5周的研究时间里持续存在。有效者(与基础值比,疼痛减轻>或=50%的患者)分别是46% (300 mg/天), 48% (600 mg/天), and 18% (安慰剂). 普瑞巴林的耐受性很好,停用率很低。最常见的副作用是头晕、嗜睡。
结论:患糖尿病周围神经病的患者,普瑞巴林可早期和持续的改善疼痛,且对睡眠有益,这通过患者积极的总体印象得到证实。在各种剂量普瑞巴林均有较好的耐受性。

13: Neurology. 2004 Dec 14;63(11):2104-10.

Pregabalin relieves symptoms of painful diabetic neuropathy: a randomized controlled trial.

Lesser H, Sharma U, LaMoreaux L, Poole RM.

University of Rochester School of Medicine & Dentistry, Rochester, NY, USA.Harold.Lesser@viahealth.org

OBJECTIVE: Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. The authors assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) vs placebo in patients with diabetic peripheral neuropathy (DPN). METHODS: Patients with a 1- to 5-year history of DPN and average weekly pain score of > or =4 on an 11-point numeric pain-rating scale were enrolled in a 5-week, double-blind, multicenter, placebo-controlled study. Patients (n = 338) were randomized to receive one of three doses of pregabalin or placebo TID. Pregabalin 600 mg/day was titrated over 6 days; lower doses were initiated on day 1. RESULTS: Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score (primary efficacy measure) vs placebo (p = 0.0001). Improvements were also seen in weekly pain score, sleep interference score, patient global impression of change, clinical global impression of change, SF-McGill Pain Questionnaire, and multiple domains of the SF-36 Health Survey. Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks. Responders (patients with > or =50% reduction in pain compared to baseline) were 46% (300 mg/day), 48% (600 mg/day), and 18% (placebo). Pregabalin was well tolerated with a low discontinuation rate. The most common adverse events were dizziness and somnolence. CONCLUSIONS: In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep, which were confirmed by positive patient global impression. Pregabalin was well tolerated at all doses.

PMID: 15596757 [PubMed - indexed for MEDLINE]

14 普瑞巴林治疗糖尿病周围神经病痛:一项随机、双盲、安慰剂对照研究

本随机、双盲、安慰剂对照、平行组、多中心、为期8周(随后进入公开阶段)的试验评估了普瑞巴林缓解糖尿病神经病理(DPN)疼痛的疗效。纳入本研究的患者需有:1-5年的DPN疼痛史,疼痛评分> or =40 mm(SF-MPQ视觉模拟量表);平均日疼痛评分> 或=4 (11分的数字疼痛评分量表 [0 = 无疼痛, 10 = 极度疼痛]).纳入研究的146名患者随机接受安慰剂(n = 70)或普瑞巴林300 mg/天 (n = 76).主要测量指标是来自患者日记的研究终点平均疼痛评分(11分的数字疼痛评分量表)。次要测量指标包括SF-MPQ评分,睡眠障碍评分,患者和临床对变化的总体印象(PGIC和CGIC), SF-36健康调查评分,POMS评分。安全评估包括:不良事件的发生率和强度,物理和神经学检查,实验室评估。与安慰剂相比,普瑞巴林显著改善平均疼痛评分(P < 0.0001),平均睡觉障碍评分(P < 0.0001); 总的SF-MPQ评分 (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); POMS 中总的情绪紊乱和紧张性焦虑成分(P < 0.03).疼痛减轻和睡眠改善在第一周出现,在研究期间显著持续(P < 0.01)。普瑞巴林与安慰剂比,虽然头晕、嗜睡的发生率更高,但耐受性良好。大多数不良反应为轻到中度,且没有因此停药。普瑞巴林对减轻DPN疼痛是安全、有效的,并且还能改善患者情绪、睡眠障碍和生活质量。

14: Pain. 2004 Aug;110(3):628-38.

Pregabalin for the treatment of painful diabetic peripheral neuropathy: a double-blind, placebo-controlled trial.

Rosenstock J, Tuchman M, LaMoreaux L, Sharma U.

Dallas Diabetes & Endo Research Center, 7777 Forest Lane, C618, Dallas, TX 75230, USA. juliorosenstock@dallasdiabetes.com

A randomized, double-blind, placebo-controlled, parallel-group, multicenter, 8-week trial (with subsequent open-label phase) evaluated the effectiveness of pregabalin in alleviating pain associated with diabetic peripheral neuropathy (DPN). For enrollment, patients must have had at baseline: 1- to 5-year history of DPN pain; pain score > or =40 mm (Short-Form McGill Pain Questionnaire [SF-MPQ] visual analogue scale); average daily pain score of > or =4 (11-point numerical pain rating scale [0 = no pain, 10 = worst possible pain]). One hundred forty-six (146) patients were randomized to receive placebo (n = 70) or pregabalin 300 mg/day (n = 76). Primary efficacy measure was endpoint mean pain score from daily patient diaries (11-point numerical pain rating scale). Secondary measures included SF-MPQ scores; sleep interference scores; Patient and Clinical Global Impression of Change (PGIC and CGIC); Short Form-36 (SF-36) Health Survey scores; and Profile of Mood States (POMS) scores. Safety assessment included incidence and intensity of adverse events, physical and neurological examinations, and laboratory evaluations. Pregabalin produced significant improvements versus placebo for mean pain scores (P < 0.0001); mean sleep interference scores SF-36 Bodily Pain subscale (P < 0.0001); total SF-MPQ score (P < 0.01); SF-36 Bodily Pain subscale (P < 0.03); PGIC (P = 0.001); and Total Mood Disturbance and Tension-Anxiety components of POMS (P < 0.03). Pain relief and improved sleep began during week 1 and remained significant throughout the study (P < 0.01). Pregabalin was well tolerated despite a greater incidence of dizziness and somnolence than placebo. Most adverse events were mild to moderate and did not result in withdrawal. Pregabalin was safe and effective in decreasing pain associated with DPN, and also improved mood, sleep disturbance, and quality of life.

PMID: 15288403 [PubMed - indexed for MEDLINE]
我先申请第一篇,谢谢
1: Clin Ther. 2007 Jan;29(1):26-48.
Pregabalin: A novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.

Tassone DM, Boyce E, Guyer J, Nuzum D.

BACKGROUND: The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is the first drug approved in the United States and in Europe for both conditions.In June 2005, pregabalin was approved as an adjunctive treatment in adults with partial-onset seizures. The FDA currently is considering the approval of pregabalin as adjunctive therapy in adults with generalized anxiety disorder (GAD) or social anxiety disorder (SAD).
OBJECTIVES: The goals of this review were to summarize the pharmacology, pharmacokinetics, efficacy, and tolerability of pregabalin; review its approved uses in the management of neuropathic pain and refractory partial-onset seizures; and investigate its potential use in patients with GAD or SAD.
METHODS: Relevant English-language literature was identified through a search of MEDLINE (1993-June 2006) and International Pharmaceutical Abstracts (2000-June 2006). The search terms included pregabalin, Lyrica, S-(+)-3 isobutylgaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008.
RESULTS: In 4 clinical trials in a total of 1068 patients with diabetic peripheral neuropathy, the patients receiving pregabalin 300 to 600 mg/d had significantly greater improvement in mean pain scores than placebo recipients (P </= 0.01). Patients with postherpetic neuralgia receiving pregabalin 450 to 600 mg/d had significantly greater improvement in relief of pain and pain-related sleep interference than placebo recipients (P </= 0.002). Patients with refractory partial-onset seizures who received pregabalin 150 to 600 mg/d (divided into 2 or 3 doses) concomitantly with antiepileptic drugs had significantly fewer seizures than placebo recipients (P </= 0.001). In the 3 studies that evaluated the efficacy of pregabalin in patients with GAD or SAD, the patients receiving pregabalin 200 to 600 mg/d (divided into 2 or 3 daily doses) had a significantly greater reduction in mean pain scores on the Hamilton Anxiety Scale than placebo recipients (P </= 0.01). Across all the reviewed clinical trials, the most commonly reported adverse effects (AEs) were those affecting the central nervous system, including somnolence (</=50%), dizziness (</=49%), and headache (</=29%). AEs resulted in withdrawal from the study in </=32% of patients.
CONCLUSIONS: Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures. The available data suggest that pregabalin may be beneficial as an adjunctive therapy in adult patients with GAD or SAD.
PMID: 17379045 [PubMed - in process]

普瑞巴林:一种治疗神经性疼痛,局部发作性癫痫和焦虑症的新γ-氨基丁酸类似物
背景:2004年12月美国食品与药品管理局(FDA) 批准普瑞巴林用于治疗糖尿病性周围神经病变的神经性疼痛和带状疱疹后遗神经痛。普瑞巴林是美国和欧洲认可的第一种适用于治疗上述两种疼痛的药。2005年6月,普瑞巴林在辅助治疗成人局灶性癫痫中得到认可。目前,美国食品与药品管理局正考虑是否批准普瑞巴林用于成人一般焦虑障碍(GAD)和社交焦虑障碍(SAD)的辅助治疗。
目的:本综述旨在概述普瑞巴林的药理学,药物代谢动力学,效能和耐受性;观察它在治疗神经性疼痛和顽固性局灶性癫痫的肯定作用;并研究它在一般焦虑障碍(GAD)和社交焦虑障碍(SAD)患者中潜在的作用。
方法:相关英文文献是在联机医学文献分析与检索系统(1993-2006,06)和国际药物摘要(2000- 2006,06)中搜索的。关键词包括普瑞巴林,Lyrica,S-(+)-3 isobutylgaba,周围神经病(PN),糖尿病性多神经病(DPN), 糖尿病性周围神经病变, 公共卫生护理(PHN),带状疱疹后遗神经痛,局部性癫痫发作,癫痫,一般焦虑障碍和CI-1008。
结果:4次临床试验中,总共有1068位糖尿病性周围神经病变患者,其中使用普瑞巴林300-600mg/d后的试验组平均疼痛评分比使用对照剂的对照组有显著的改善(P </= 0.01)。带状疱疹后遗神经痛患者使用了普瑞巴林450-600 mg/d治疗组在疼痛和疼痛性睡眠干扰缓解方面比对照组有显著改善(P </= 0.002)。顽固性局灶性癫痫患者使用普瑞巴林150-600 mg/d(2-3次/天)合并抗癫痫剂治疗的试验组比对照组癫痫发作明显减少(P </= 0.001)。在3次旨在评价普瑞巴林在治疗一般焦虑障碍(GAD)和社交焦虑障碍(SAD)中效能的研究中,使用普瑞巴林200-600 mg/d(分2-3次/天)组较对照组在Hamilton焦虑量表平均疼痛评分显著减少(P </= 0.01)。通过所有这些临床实验观察,普瑞巴林最常见的不良反应(AEs)是影响中枢神经系统,表现为嗜睡(</=50%)、头昏 (</=49%)和头痛(</=29%)。研究中,有</=32%的患者不良反应会消退。
结论:普瑞巴林是糖尿病性周围神经病变,带状疱疹后遗神经痛和成人局灶性癫痫的一种有效治疗药物。有文献表明普瑞巴林辅助治疗成人一般焦虑障碍(GAD)和社交焦虑障碍(SAD)中可能有作用。
我认领第4篇,谢谢!
斑竹您好,我认领第五篇
领2。9
surgeond战友、chen200829战友的申领为无效申领
感谢两位战友的积极参与,期待二位战友在麻醉疼痛版的精彩表现

请yuanliyong战友重新选择申领题号,第二篇rena_liu申领有效
请大家严格按照相关章程操作

具体规则见
>
斑竹您好,我认领第4和第9篇!
对不起,刚到没经验.其是我还翻译了第4篇了,能允许我上传吗? .
1.普瑞巴林:一种类似GABA的治疗神经病理性痛,癫痫部分性发作和焦虑症的新药

背景:2004年12月,美国食品药品管理局(FDA)批准普瑞巴林用于治疗糖尿病外周神经病变性疼痛和后遗神经痛。它是第一个获准在欧洲和美国治疗这两种疼痛的药物。2005年6月,普瑞巴林获准用于成人癫痫部分性发作的辅助治疗。现在,FDA正在考虑批准普瑞巴林用于广泛性焦虑症(GAD)或社交焦虑症(SAD)的辅助治疗。
目的:本综述旨在归纳普瑞巴林的药理、药代、药效和耐受性,回顾其获准用于神经病理性痛和难治性癫痫部分性发作的治疗,并且探讨其用于广泛性焦虑症和社交焦虑症的可能性。
方法:检索MEDLINE(1993-2006.06) 和国际药学文摘(2000-2006.06)上的相关英文文献,检索词如下:普瑞巴林、Lyrica、S-(+)-3 isobutylgaba、后遗神经痛(PN)、糖尿病周围神经痛(DPN)、糖尿病外周神经病变、带状疱疹后神经痛(PHN)、后遗神经痛(postherpetic neuralgia)、癫痫部分性发作、癫痫、广泛性焦虑症和CI-1008。
结果:在共有1068名糖尿病外周神经病变患者的四项临床试验中,接受普瑞巴林300~600mg/天治疗的患者与安慰剂组相比,平均疼痛评分显著改善(P≤0.01)。采用普瑞巴林450~600mg/天治疗的后遗神经痛患者,与安慰剂组相比,其疼痛和疼痛相关性睡眠干扰均明显改善(P≤0.002)。采用普瑞巴林150~600mg/天(分为2次或3次剂量)联合抗癫痫药物治疗难治性癫痫部分性发作,与安慰剂组相比,其发作次数显著减少(P≤0.001)。在评估普瑞巴林治疗GAD和SAD有效性的三项研究中,接受该药200~300mg/天(分为2次或3次剂量)的患者与安慰剂组相比,Hamilton焦虑量表的平均得分显著下降(P≤0.01)。通过所回顾的临床试验发现,影响中枢神经系统是最常见的副作用,包括困倦(≤50%),头昏(≤49%)和头痛(≤29%)。副作用导致部分患者(≤32%)退出了研究。
结论:普瑞巴林可有效治疗糖尿病周围神经痛、后遗神经痛和成人难治性癫痫部分性发作。目前的数据也提示,普瑞巴林有助于成人GAD和SAD的辅助治疗。

1: Clin Ther. 2007 Jan;29(1):26-48.

Pregabalin: A novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders.

Tassone DM, Boyce E, Guyer J, Nuzum D.

BACKGROUND:: The US Food and Drug Administration (FDA) approved pregabalin in December 2004 for the treatment of neuropathic pain associated with diabetic peripheral neuropathy and postherpetic neuralgia. Pregabalin is the first drug approved in the United States and in Europe for both conditions. In June 2005, pregabalin was approved as an adjunctive treatment in adults with partial-onset seizures. The FDA currently is considering the approval of pregabalin as adjunctive therapy in adults with generalized anxiety disorder (GAD) or social anxiety disorder (SAD). OBJECTIVES:: The goals of this review were to summarize the pharmacology, pharmacokinetics, efficacy, and tolerability of pregabalin; review its approved uses in the management of neuropathic pain and refractory partial-onset seizures; and investigate its potential use in patients with GAD or SAD. METHODS:: Relevant English-language literature was identified through a search of MEDLINE (1993-June 2006) and International Pharmaceutical Abstracts (2000-June 2006). The search terms included pregabalin, Lyrica, S-(+)-3 isobutylgaba, PN, DPN, diabetic peripheral neuropathy, PHN, postherpetic neuralgia, partial seizures, epilepsy, generalized anxiety disorder, and CI-1008. RESULTS:: In 4 clinical trials in a total of 1068 patients with diabetic peripheral neuropathy, the patients receiving pregabalin 300 to 600 mg/d had significantly greater improvement in mean pain scores than placebo recipients (P </= 0.01). Patients with postherpetic neuralgia receiving pregabalin 450 to 600 mg/d had significantly greater improvement in relief of pain and pain-related sleep interference than placebo recipients (P </= 0.002). Patients with refractory partial-onset seizures who received pregabalin 150 to 600 mg/d (divided into 2 or 3 doses) concomitantly with antiepileptic drugs had significantly fewer seizures than placebo recipients (P </= 0.001). In the 3 studies that evaluated the efficacy of pregabalin in patients with GAD or SAD, the patients receiving pregabalin 200 to 600 mg/d (divided into 2 or 3 daily doses) had a significantly greater reduction in mean pain scores on the Hamilton Anxiety Scale than placebo recipients (P </= 0.01). Across all the reviewed clinical trials, the most commonly reported adverse effects (AEs) were those affecting the central nervous system, including somnolence (</=50%), dizziness (</=49%), and headache (</=29%). AEs resulted in withdrawal from the study in </=32% of patients. CONCLUSIONS:: Pregabalin appears to be an effective therapy in patients with diabetic peripheral neuropathy, postherpetic neuralgia, and adults with refractory partial-onset seizures. The available data suggest that pregabalin may be beneficial as an adjunctive therapy in adult patients with GAD or SAD.
PMID: 17379045 [PubMed - in process]

5.口服普瑞巴林和阿瑞吡坦在电刺激致痛敏和中枢敏化志愿者的作用

背景:中枢敏化是神经病理性痛的一个重要机制,它的人类模型有助于早期检验新疗法的有效性。通过反复的电刺激皮肤,可以导致痛敏和中枢敏化以制造模型。为评估其预期价值,我们采用了普瑞巴林和阿瑞吡坦两种药物,前者是神经病理性痛的标准治疗,后者是一种NK1拮抗剂,对神经病理性痛患者无效而在动物模型中有效。另外,我们还采用与COX-2抑制剂帕瑞考昔联合用药,探讨是否可增加其作用。
方法:这是一项双盲、两阶段、安慰剂对照的研究,采用不完全区组设计。32名健康志愿者在测试前口服普瑞巴林(调定至300mg)或阿瑞吡坦(调定至320mg)或者相应的安慰剂,共六天。确认中枢敏化3小时,在2小时时予静脉注射帕瑞考昔(40mg)或生理盐水。
结果:普瑞巴林与安慰剂相比,可显著减小点触痛敏和非伤害性接触异常疼痛的范围(两者均P < 0.0001);而阿瑞吡坦与安慰剂无统计学差异。与安慰剂+帕瑞考昔组相比,普瑞巴林+帕瑞考昔治疗组异常性疼痛的范围显著减小(P < 0.0001),而痛敏的范围未明显减小(P = 0.09);阿瑞吡坦+帕瑞考昔组则未有任何改善。
结论:该模型可用于早期预见止痛方法的有效性和研究其机制。也可用于探讨联合止痛的有效性,以阐明(中枢敏化?)基本机制。

5: Br J Anaesth. 2007 Feb;98(2):246-54.

Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers.

Chizh BA, Gohring M, Troster A, Quartey GK, Schmelz M, Koppert W.

Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2GG, UK. boris_a_chizh@gsk.com

BACKGROUND: Central sensitization is an important mechanism of neuropathic pain; its human models could be useful for early detection of efficacy of novel treatments. The electrical hyperalgesia model invokes central sensitization by repetitive stimulation of the skin. To assess its predictive value, we have investigated pregabalin, a standard neuropathic pain treatment, and aprepitant, an NK(1) antagonist, as an example of a drug class active in animal models but not in neuropathic pain patients. Furthermore, we explored if combinations of either of these drugs with the COX-2 inhibitor parecoxib could improve its efficacy. METHODS: This was a double-blind, two-period, placebo-controlled study using incomplete block design. Thirty-two healthy volunteers received either oral pregabalin (titrated to 300 mg) or aprepitant (titrated to 320 mg), or matching placebo over 6 days before testing. Sensitization was assessed over 3 h; at 2 h, subjects received either parecoxib (40 mg) or saline i.v. RESULTS: Pregabalin significantly reduced the areas of punctate mechanical hyperalgesia and dynamic touch allodynia vs placebo (both P < 0.0001); no significant reduction in the area of hyperalgesia or allodynia vs placebo was observed with aprepitant. In the pregabalin + parecoxib treated group, the area of allodynia was significantly reduced (P < 0.0001) and the area of hyperalgesia insignificantly attenuated (P = 0.09) vs placebo + parecoxib; no efficacy improvement was observed with aprepitant + parecoxib. CONCLUSIONS: The model can serve to predict analgesic efficacy in early human development and investigate the mechanism of action. The model could also be used to explore efficacy of analgesic combinations to provide a rationale for patient studies.

PMID: 17251214 [PubMed - indexed for MEDLINE]
已全部认领和分配完毕,希望大家能够定期完成任务。
需要说明的是
1 surgeond是新战友,热烈欢迎你,但请你仔细阅读活动规则后参与进来
2 请 llc168认领第9篇
3 请yuanliyong认领第4篇
4 对于积极参与校对者,也将予以鼓励
4: J Pain. 2007 Feb 8;
Pregabalin Reduces Muscle and Cutaneous Hyperalgesia in Two Models of Chronic Muscle Pain in Rats. [llc168战友已申领]

2 请 llc168认领第9篇
风雨同版主您好,请问具体是哪一篇啊?我译第4篇了啊.
8.癫痫
普瑞巴林的药理作用及机制:钙通道α2-δ亚基作为抗癫痫药物作用耙点被发现.
普瑞巴林(lyrica)是一种新的在动物癫痫模型中效果很好的新的抗癫痫药物. 普瑞巴林批准在美国和欧洲为成年人部分癫痫发作的辅助治疗,并已批准用于成年人治疗糖尿病神经疼痛或带状疱疹后神经痛. 最近, 在欧洲又被批准治疗焦虑症. 普瑞巴林结构和抗癫痫药物加巴喷址相似,并且作用部位一致,即 α2-δ蛋白质,即电压门控钙通道的辅助亚基. 普瑞巴林精细地降低神经突触数种神经递质的释放,显然通过结合α2-δ亚基. 其可能通过减少体内神经兴奋和减少发作. 多项研究显示普瑞巴林发挥药理作用需要结合α2-δ亚基、 包括结合α2-δ亚基化合物的构效分析和通过对α2-δ1蛋白质缺乏约束力的基因缺陷小鼠的药理作用. 迄今为止的临床前研究结果一致的机制可能是通过降低递质释放从而减少可能导致的神经异常兴奋. 这次回顾显示了普瑞巴林的临床前药理,也即高亲和力结合位点生物学和假定作用位点.
8: Epilepsy Res. 2007 Feb;73(2):137-50. Epub 2006 Nov 28.

Pharmacology and mechanism of action of pregabalin: the calcium channel alpha2-delta (alpha2-delta) subunit as a target for antiepileptic drug discovery.

Taylor CP, Angelotti T, Fauman E.

Department of CNS Biology, Pfizer Global Research & Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. charles.taylor@pfizer.com

Pregabalin (Lyrica) is a new antiepileptic drug that is active in animal seizure models. Pregabalin is approved in US and Europe for adjunctive therapy of partial seizures in adults, and also has been approved for the treatment of pain from diabetic neuropathy or post-herpetic neuralgia in adults. Recently, it has been approved for treatment of anxiety disorders in Europe.. Pregabalin is structurally related to the antiepileptic drug gabapentin and the site of action of both drugs is similar, the alpha2-delta (alpha2-delta) protein, an auxiliary subunit of voltage-gated calcium channels. Pregabalin subtly reduces the synaptic release of several neurotransmitters, apparently by binding to alpha2-delta subunits, and possibly accounting for its actions in vivo to reduce neuronal excitability and seizures. Several studies indicate that the pharmacology of pregabalin requires binding to alpha2-delta subunits, including structure-activity analyses of compounds binding to alpha2-delta subunits and pharmacology in mice deficient in binding at the alpha2-delta Type 1 protein. The preclinical findings to date are consistent with a mechanism that may entail reduction of abnormal neuronal excitability through reduced neurotransmitter release. This review addresses the preclinical pharmacology of pregabalin, and also the biology of the high affinity binding site, and presumed site of action.
PMID: 17126531 [PubMed - in process]

10.疼痛
加巴喷、普瑞巴林用于治疗神经痛:实验室和临床实验数据的回顾.
加巴喷(neurontin、加拿大辉瑞公司)、普瑞巴林(lyrica, 加拿大辉瑞公司)最初作为抗癫痫药物,后来发现可有效治疗神经痛,创造了比较新一类镇痛药. 文章回顾了本实验室的数据和这些药物在动物模型上治疗神经痛的效果, 各种神经痛综合征患者的治疗效果的临床试验数据. 实验室的证据表明,加巴喷和普瑞巴林能抑制过敏及各种神经损伤引起的痛觉过敏和异常性疼痛, 包括周边外伤,糖尿病和化疗. 目前,这些意见认为止痛效果出现是因为药物与电压门钙通道α2-δ亚基的相互作用. 大多数临床证据肯定带状疱疹后神经痛、糖尿病神经病的镇痛效果、 而有限的证据显示此功效可延伸到其它的,但不一定所有神经痛症状. 从早期的比较试验及 荟萃分析集合估计显示,加巴喷和普瑞巴林镇痛功效或许稍低于三环抗忧郁药或阿片. 不过, 两种药物最具吸引力的地方包括其耐受性,无毒性,好用. 今后研究工作是需要充分认识这些药物的作用机制, 明确加巴喷和普瑞巴林在各临床症状神经痛中的安全性和疗效、 并进一步探讨这些药物在合理的神经性痛药理学中的作用.
10: Pain Res Manag. 2006 Summer;11 Suppl A:16A-29A.

Gabapentin and pregabalin for the treatment of neuropathic pain: A review of laboratory and clinical evidence.

Gilron I, Flatters SJ.

Queen's University, Kingston, Canada.

Gabapentin (Neurontin, Pfizer Canada Inc) and pregabalin (Lyrica, Pfizer Canada Inc) were initially developed as antiepileptic drugs and were later discovered to be effective in the treatment of neuropathic pain, creating a relatively novel class of analgesic drugs. The present article reviews the laboratory data on the antinociceptive effects of these drugs in animal models of neuropathic pain, and the clinical trial data on their effects in patients with various neuropathic pain syndromes. Laboratory evidence suggests that both gabapentin and pregabalin can inhibit hyperalgesia and allodynia evoked by a variety of neural insults, including peripheral trauma, diabetes and chemotherapy. Current opinion suggests these antinociceptive effects occur because of drug interaction with the alpha2delta subunit of voltage-gated calcium channels. The majority of clinical evidence supports analgesic efficacy in diabetic neuropathy and postherpetic neuralgia, and limited evidence suggests that this efficacy extends to other, but not necessarily all, neuropathic pain syndromes. Early comparative trials and pooled estimates from meta-analyses suggest that analgesic efficacy of gabapentin and pregabalin is perhaps slightly lower than that of tricyclic antidepressants or opioids. However, the most attractive aspects of these two drugs include their tolerability, lack of serious toxicity and ease of use. Future research efforts are warranted to fully understand the mechanism of action of these drugs, to clearly characterize the safety and efficacy of gabapentin and pregabalin in all clinical neuropathic pain syndromes, and to further explore the role of these drugs in the rational polypharmacy of neuropathic pain.

PMID: 16755322 [PubMed - in process]
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2.慢性压迫性损伤时普瑞巴林在同侧脊背角结合增加。
译者:rena_liu
普瑞巴林(γ氨基丁酸3取代基类似物)近来已经被批准用于治疗神经源性疼痛。我们研究了慢性压迫性损伤(CCI)时[(3)H]普瑞巴林解剖结合轮廓,并且同利用原位杂交表达的α2δ亚单位相比较。我们在此报道了在慢性压迫性损伤时普瑞巴林在同侧脊背角结合的强度和分布结构被改变,并且这些伴随着同侧背根神经节(DRG)α2δmRNA 的相应的增加。很有可能DRG mRNA 生成增加导致α2δ蛋白的合成增多和相应的运输到脊背角也增加。假使感觉神经的异常活动可能明显影响神经痛的症状,那么将可观察到钙通道亚单位和蛋白在中央末端的表达。对于神经源性疼痛患者普瑞巴林结合位点的上调可能导致对神经损伤的反应的分离,因此其作用机理可能归因于普瑞巴林在这些位点由优先发挥作用。

2: Neurosci Lett. 2007 Mar 2;

[(3)H] pregabalin binding is increased in ipsilateral dorsal horn following chronic constriction injury.

Melrose HL, Kinloch RA, Cox PJ, Field MJ, Collins D, Williams D.

Pain Therapeutics, Discovery Biology, Pfizer Global Research and Development,Ramsgate Road, Sandwich, Kent CT13 9NJ, United Kingdom.

Pregabalin, a 3-substituted analogue of gamma-amino butyric acid has recently been approved for treatment of neuropathic pain. We have investigated the anatomical binding profile of [(3)H] pregabalin following chronic constriction injury (CCI) and compared this with alpha2delta1 subunit expression using in situ hybridisation. We report here that the intensity and distribution pattern of [(3)H] pregabalin binding is altered in the ipsilateral dorsal horn following CCI and this is associated with a corresponding increase in alpha2delta1 mRNA in the ipsilateral dorsal root ganglion (DRG). It is likely that increased DRG mRNA production leads to increased alpha2delta1 protein production and subsequent transport by primary afferents to the dorsal horn. The increased expression of calcium channel subunits and protein in central terminals is interesting, given that abnormal activity within sensory nerves is likely to significantly contribute to the symptomatology of neuropathic pain. The upregulation of pregabalin binding sites in sensory nerve terminals may occur as part of the response to nerve damage in neuropathic pain patients, and therefore, preferential actions of pregabalin at these sites may contribute to its mechanism of action in man.
3.在交感神经维持性疼痛和交感神经无关性疼痛鼠模型中普瑞巴林的抗疼痛超敏的效果
译者:rena_liu
普瑞巴林与电压依赖的钙通道α2δ亚单位结合,调整神经递质的释放,从而对神经源性疼痛起到止痛效果。神经源性疼痛包括交感神经维持性疼痛( SMP)和交感神经无关性疼痛(SIP)。我们研究普瑞巴林在SMP和 SIP占优势的神经源性疼痛模型中对触觉异常性疼痛(TA)和冷感觉异常性疼痛(CA)的抗痛觉超敏的效果。通过结扎L5 和L6脊神经(SMP模型)或通过横断胫骨和腓肠神经(SIP模型)形成痛觉超敏。为便于鞘内给药,一个PE-10导管通过寰枕膜植入到腰部膨大。普瑞巴林通过腹膜内或鞘内给药剂量逐渐增加直到产生抗痛觉超敏作用或出现运动受损。TA通过用von Frey 细丝评估,CA通过滴丙酮的方法来评估。腹膜内给药普瑞巴林剂量依赖的缓解两个模型中的TA和SMP模型中的CA,但对SIP模型中的CA并不起作用。鞘内注射普瑞巴林可剂量依赖的缓解两个模型中的TA和CA。然而,SMP模型中普瑞巴林鞘内给药的剂量效应曲线较之SIP的左偏并且在SMP中普瑞巴林鞘内给药治疗CA的ED50至少是SIP的900倍。这些发现表明普瑞巴林主要通过作用于脊髓神经束起到抗疼痛超敏的作用,并且鞘内注射该药对于SMP产生更有效的抗疼痛超敏的作用。对于SIP中的CA可能很少涉及到α2δ亚单位的作用。

3: Yonsei Med J. 2007 Feb 28;48(1):41-7.

Antiallodynic effect of pregabalin in rat models of sympathetically maintained and sympathetic independent neuropathic pain.

Han DW, Kweon TD, Lee JS, Lee YW.

Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Kangnam-gu, Seoul 135-720, Korea.

Pregabalin binds to the voltage-dependent calcium channel alpha2delta subunit and modulates the release of neurotransmitters, resulting in analgesic effects on neuropathic pain. Neuropathic pain has both sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) components. We studied the antiallodynic effects of pregabalin on tactile allodynia (TA) and cold allodynia (CA) in SMP-and SIP-dominant neuropathic pain models. Allodynia was induced by ligation of the L5 and L6 spinal nerves (SMP model) or by transection of the tibial and sural nerves (SIP model) in rats. For intrathecal drug administration, a PE-10 catheter was implanted through the atlantooccipital membrane to the lumbar enlargement. Pregabalin was administered either intraperitoneally (IP) or intrathecally (IT) and dosed up incrementally until an antiallodynic effect without sedation or motor impairment was apparent. TA was assessed using von Frey filaments, and CA was assessed using acetone drops. IP-administered pregabalin dose-dependently attenuated TA in both models and CA in the SMP model, but not CA in the SIP model. IT-administered pregabalin dose-dependently attenuated both TA and CA in both models. However, the dose response curve of IT-administered pregabalin in SMP was shifted to left from that of SIP and the ED50 of IT-administered pregabalin for CA in SMP was about 900 times less than that in SIP. These findings suggest that pregabalin exerts its antiallodynic effect mainly by acting at the spinal cord, and that IT-administered pregabalin has more potent antiallodynic effects in SMP. The alpha2delta subunit might be less involved in the CA in SIP.
4.在两种慢性肌肉痛的老鼠模型中,普瑞巴林可减轻肌肉和皮肤的痛觉过敏
译者ID:llc168

爱荷华州爱荷华市爱荷华大学康复和理疗科学的毕业生规划。

普瑞巴林常用于的治疗神经性疼痛。当前研究是评估普瑞巴林在两种肌肉诱导的痛觉过敏老鼠模型(炎症性和非炎症性)中的效应。在痛觉过敏诱导前及诱导后、普瑞巴林治疗(saline, 10 to 100 mg/kg i.p.)后都测量肌肉痛觉过敏(压迫肌肉的退缩阈值)和爪子的皮肤痛觉过敏(von Frey filaments的退缩阈值)。在炎症性模型中,将3%的爱兰苔胶注入一腓肠肌肌肉,2周后可以双侧性的降低爪子的机械退缩阈值和降低同侧腓肠肌的压迫退缩阈值。与媒介物对照,普瑞巴林(10 to 100 mg/kg)可增加炎症性的肌肉的压迫退缩阈值。当剂量达100 mg/kg时,普瑞巴林也可以双侧性的增加爪子的机械退缩阈值。在非炎症性模型中,向单侧腓肠肌注射酸性saline液2次,在第二次注射后24小时,可产生双侧皮肤和肌肉痛觉过敏。与媒介对照相比,普瑞巴林(10 to 100 mg/kg i.p.)可显著的双侧性的增加爪子肌肉的压迫退缩阈值和机械退缩阈值。然而,普瑞巴林在高剂量时(60 to 100 mg/kg)还有显著的动力效应。因此,在不产生共济失调的剂量下,普瑞巴林可以减轻2种动物模型中肌肉损伤后发生的肌肉和皮肤痛觉过敏。前景:这项研究表明普瑞巴林可以减轻炎症性和非炎症性肌肉痛模型中的皮肤和肌肉痛觉过敏。因此,普瑞巴林可能成为慢性肌肉疼痛病人的一种有效治疗药物。
PMID: 17293165 [PubMed - as supplied by publisher]
注:关于von Frey filaments的知识可以看看这个网:e, pregabalin had no effect on contraction from direct stimulation of muscle, suggesting a lack of drug effects on contraction coupling. Our data are consistent with pregabalin having no effect on striated muscle L-type calcium channel function. However, in mice expressing mutant (R217A) alpha(2)-delta Type 1, there was no significant effect of pregabalin on nerve-evoked muscle contraction. We propose that pregabalin reduces presynaptic neurotransmitter release without altering postsynaptic receptors or contraction coupling and that these effects require high affinity binding to alpha(2)-delta Type 1 auxiliary subunit of presynaptic voltage-gated calcium channels.

PMID: 17064682 [PubMed - indexed for MEDLINE]

普瑞巴林突触作用模式:小鼠实验中,结合于突触前钙通道α2-δ亚基减少神经递质传递
欧洲药理学杂志2006 Dec 28;553(1-3):82-8.
在欧洲和美国,普瑞巴林已被批准用于治疗某些类型的外周神经病理性疼痛和部分发作性癫痫的辅助治疗;在欧洲也被用于治疗一般焦虑症。尽管已经明确普瑞巴林选择性的结合于压力门控钙通道辅助性α2-δ亚基,但普瑞巴林作用的具体细胞定位尚不明确。骨骼肌纤维上存在的高密度的α2-δ亚基是我们有理由提出疑问:普瑞巴林是否能改变兴奋收缩偶联。我们采用富含人工基因突变的α2-δ1型蛋白(R217A)的小鼠比目鱼肌神经肌肉接头,作为检测普瑞巴林的作用机制模型。在野生小鼠中,临床常用浓度(10 muM)的普瑞巴林能使神经诱发的肌肉收缩减少16%,当用箭毒阻断了乙酰胆碱受体以后,普瑞巴林对直接刺激诱发的肌肉收缩没有(抑制)作用,提示药物对兴奋收缩偶联没有了作用。我们的实验结果与普瑞巴林对横纹肌L型钙通道无作用一致。然而,在人工基因突变型富含α2-δ1型蛋白(R217A)的小鼠中,普瑞巴林对肌肉兴奋收缩偶联没有显著影响。我们猜想,普瑞巴林仅仅抑制突触前神经递质的释放而不改变突触后受体和兴奋收缩偶联,这就需要普瑞巴林对突触前钙通道α2-δ亚基具有高度亲和力才能实现。
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