共识易览:带状疱疹后神经痛如何管理?

2016-04-18 指南君 中国疼痛医学杂志

带状疱疹后神经痛 (PHN)定义为带状疱疹 (HZ) 皮疹愈合后持续1 个月及以上的疼痛,是带状疱疹最常见的并发症。PHN 是最常见的一种神经病理性疼痛,可表现为持续性疼痛,也可缓解一段时间后再次出现。近日,我国发布了《带状疱疹后神经痛诊疗中国专家共识》,指南君将主要内容整理如下。 主要内容 一、流行病学 带状疱疹和PHN 的发病率及患病率均有随年龄增加而

带状疱疹后神经痛 (PHN)定义为带状疱疹 (HZ) 皮疹愈合后持续1 个月及以上的疼痛,是带状疱疹最常见的并发症。PHN 是最常见的一种神经病理性疼痛,可表现为持续性疼痛,也可缓解一段时间后再次出现。近日,我国发布了《带状疱疹后神经痛诊疗中国专家共识》,指南君将主要内容整理如下。

主要内容

一、流行病学


带状疱疹和PHN 的发病率及患病率均有随年龄增加而逐渐升高的趋势,60 岁及以上的带状疱疹患者约65% 会发生PHN,70 岁及以上者可达75%。PHN的危险因素见表1。



二、发病机制

带状疱疹的病原体是水痘-带状疱疹病毒(VZV)沿感觉神经侵入脊神经节或脑神经感觉神经节内并潜伏,当机体免疫功能低下时,潜伏的病毒再活化,大量复制并沿感觉神经纤维向所支配的皮节扩散,发生带状疱疹。
 
PHN的发生机制目前不完全明了,神经可塑性是PHN 产生的基础,其机制可能涉及:外周敏化、中枢敏化、炎性反应、去传入。
 

三、临床表现


带状疱疹后神经痛特点如下:

部位常见于单侧胸部、三叉神经(主要是眼支)或颈部,其中胸部占50%,头面部、颈部及腰部分别各占10%~20%,骶尾部占2%~8%,其他部位< 1%。
 
疼痛性质多样,可为烧灼样、电击样、刀割样、针刺样或撕裂样。
 
疼痛特征为自发痛、痛觉超敏、感觉异常。30%~50% 患者的疼痛持续超过1 年,部分病程可达10 年或更长。
 

四、诊断及鉴别诊断


PHN 的诊断步骤见表2。诊断主要依据带状疱疹病史和临床表现,一般无需特殊的实验室检查或其他辅助检查。

需要鉴别诊断的疾病包括原发性三叉神经痛、舌咽神经痛、颈神经痛、肋间神经痛、脊柱源性胸痛、椎体压缩后神经痛、脊神经根性疼痛和椎体肿瘤转移性疼痛等。
 


五、治疗

PHN 治疗目的是:尽早有效地控制疼痛,缓解伴随的睡眠和情感障碍,提高生活质量。

1、 药物治疗

本共识推荐治疗PHN 的一线药物包括钙离子通道调节剂(普瑞巴林和加巴喷丁)、三环类抗抑郁药(阿米替林)和5% 利多卡因贴剂,二线药物包括阿片类药物和曲马多。

(1)钙通道调节剂(普瑞巴林、加巴喷丁)

加巴喷丁和普瑞巴林可与电压门控钙离子通道(VGCC) 的α2-δ 亚基结合,减少兴奋性神经递质的过度释放,抑制痛觉过敏和中枢敏化。

加巴喷丁的起始剂量为每日300 mg,常用有效剂量为每日900~3600 mg,患者有肾功能不全的应减量,主要不良反应为嗜睡和头晕,需要数周缓慢滴定至有效剂量。

普瑞巴林是第二代钙离子通道调节剂,。普瑞巴林剂量每日为150~600 mg,滴定期5~7 天。在肾功能不全的患者中应减量。不良反应与加巴喷丁相似。

为避免头晕和嗜睡,两药均应遵循:夜间起始、逐渐加量和缓慢减量的原则。
 
(2)三环类抗抑郁药(TCAs)

三环类抗抑郁药通过阻断突触前膜去甲肾上腺素和5-羟色胺的再摄取,阻断电压门控钠离子通道和α 肾上腺素受体,调节疼痛传导下行通路,发挥镇痛作用。
最常用的药物为阿米替林,首剂应睡前服用,每次12.5~25 mg,根据患者反应可逐渐增加剂量,每日最大剂量150 mg。应注意其心脏毒性,有缺血性心脏病或心源性猝死风险的患者应避免使用。青光眼、尿潴留、自杀等高风险患者应慎用。此外,该药可能导致或加重认知功能障碍和步态异常。老年患者发生的不良反应风险高,使用过程中要加强监测。
 
(3)利多卡因贴剂利

多卡因阻断电压门控钠离子通道,减少损伤后初级传入神经的异位冲动,从而减少PHN 患者痛觉。利多卡因贴剂起效快( ≤ 4 h)。在为期4~12 周的临床研究中,有约1/4~1/3 的患者疼痛缓解≥ 50%。对利多卡因贴剂或普瑞巴林单药治疗无效的PHN 患者,采用利多卡因贴剂和普瑞巴林联合治疗可以有效缓解疼痛。利多卡因贴剂最常见的不良反应包括使部位皮肤反应,如短暂瘙痒、红斑和皮炎。
 
(4)曲马多

曲马多可显著缓解PHN 的烧灼痛、针刺痛及痛觉超敏现象,但对闪电样、刀割样疼痛效果不明显,其疗效弱于强阿片类药物,而耐受性优于强阿片类药物。不良反应与剂量相关,包括恶心、呕吐、头晕、便秘、尿潴留、嗜睡和头痛等。应遵循低剂量开始,缓慢逐渐加量的原则。

起始剂量每次25~50 mg、每日1~2 次,每日最大量400 mg。应注意选择控释或缓释剂型,并且不与5-羟色胺药物(包括SNRIs)同时使用,以避免5- 羟色胺综合征风险。该药滥用率低,但也会发生药物依赖,需逐步停药。
 
(5)阿片类镇痛药

研究表明阿片类镇痛药可以有效治疗PHN 的烧灼痛、针刺痛及痛觉超敏,考虑到误用和滥用的风险及耐药的产生,推荐阿片类镇痛药作为二线治疗药物。常用药物有吗啡、羟考酮和芬太尼等。阿片类镇痛药治疗PHN 应遵循以下原则:在恰当的治疗目标和密切监测下处方阿片类药物,并严格选择控缓释剂型;小剂量开始治疗,定期评估疗效和安全性;一旦治疗无效,应立即停药,一般使用不超过8 周。阿片类药物的不良反应包括恶心、呕吐、过度镇静、呼吸抑制等,在用药后1~2 周内可能发生耐受。
 
(6)其他药物

临床上还应用5-羟色胺和去甲肾上腺素再摄取抑制药 (SNRIs) 来治疗PHN,代表药物有文拉法辛和度洛西汀,但缺乏大型随机对照研究证据。
 
牛痘疫苗接种家兔皮肤炎症提取物、局部辣椒素、其他抗癫痫药(拉莫三嗪、丙戊酸钠、托吡酯)及草乌甲素也被用来治疗PHN。

2、微创介入治疗

(1)神经介入技术

①神经阻滞:在相应神经根、干、节及硬膜外注入局麻药或以局麻药为主的药物以短暂阻断神经传导功能,既能达到治疗作用,又对神经无损伤。

目前得到广泛认可的神经阻滞用药主要包括局部麻醉药和糖皮质激素等。

②选择性神经毁损:以手术切断或部分切断,或用化学方法(乙醇和阿霉素)或物理方法(射频热凝和冷冻等)阻断脑、脊神经、交感神经及各类神经节等的神经传导功能,神经毁损为不可逆的治疗。

③鞘内药物输注治疗:通过埋藏在患者体内的药物输注泵,将泵内的药物输注到患者的蛛网膜下腔,直接作用于脊髓或中枢,达到控制疼痛的目的。常见的药物包括阿片类药物、局麻药等,其中吗啡的临床应用最广。

(2)神经调控技术

①脉冲射频治疗:脉冲射频是一种神经调节治疗,通常使用频率2 Hz、电压45 V,电流持续时间20 ms,间歇期480 ms 的脉冲式射频电流进行治疗,脉冲射频可以影响感觉神经ATP 代谢以及离子通道的功能,持续、可逆地抑制C 纤维兴奋性传入,从而对相关神经的痛觉传导起到阻断作用。

脉冲射频对神经纤维结构无破坏作用,能改善疼痛,提高生活质量。治疗后也较少发生感觉减退、酸痛、灼痛及运动神经损伤,较多的应用于带状疱疹后遗神经痛的治疗。

②神经电刺激:目前临床上使用的神经电刺激方法包括脊髓电刺激 (SCS),外周神经刺激 (PNS) 和经皮神经电刺激 (TENS) 等。

3、其他治疗

针刺治疗、臭氧治疗等技术在临床上显示有一定的效果。在PHN 患者中很大部分伴有抑郁症或焦虑症,治疗方案中需要重视及联合心理治疗及行为调节。

以上内容为指南君学习笔记,整理自《带状疱疹后神经痛诊疗中国专家共识》,中国疼痛医学杂志.2016,22(3):161-167.

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    2017-06-20 戒馋,懒,贪

    看过几个后遗神经痛的患者,也做过阻滞和鞘内阻滞,感觉效果不好,不知道神经电刺激治疗效果怎么样

    0

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    2016-09-15 1e10c84am36(暂无匿称)

    文章不错,值得拜读

    0

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    2016-04-22 木水晶

    刚好有个疱疹后神经痛的病人,很实用!

    0

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    2016-04-20 贵阳
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    2016-04-19 李继凯

    学习了…

    0

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    2016-04-19 李继凯

    写的不错

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=213025, encodeId=95c5213025a2, content=看过几个后遗神经痛的患者,也做过阻滞和鞘内阻滞,感觉效果不好,不知道神经电刺激治疗效果怎么样, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM7GibvIBibibnnnvpajk2stlDF5oichYahI6Bia8uxeTBFoPbdoHWebyXf9eal9FNgUF2lNcrwoZicM3BvQ/0, createdBy=a3742066385, createdName=戒馋,懒,贪, createdTime=Tue Jun 20 08:19:33 CST 2017, time=2017-06-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1691647, encodeId=06b9169164e57, content=<a href='/topic/show?id=fa8148552d5' target=_blank style='color:#2F92EE;'>#带状疱疹后神经痛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=48552, encryptionId=fa8148552d5, topicName=带状疱疹后神经痛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=213529278967, createdName=jeanqiuqiu, createdTime=Thu Sep 08 22:50:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127120, encodeId=dae012e12038, content=文章不错,值得拜读, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Thu Sep 15 07:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=80659, encodeId=40b98065910, content=刚好有个疱疹后神经痛的病人,很实用!, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/DYAIOgq83er7gGJY7ibia1wDTTwTL7vXbqvekMBTHAsd3KZ7btXM9tnHuicI2LdxJtIiccXeDCiaTvzkwMuribZ9oHVA/0, createdBy=c7b81713099, createdName=木水晶, createdTime=Fri Apr 22 14:30:00 CST 2016, time=2016-04-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1540808, encodeId=9bf51540808d9, content=<a href='/topic/show?id=ac8de440615' target=_blank style='color:#2F92EE;'>#神经痛#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=74406, encryptionId=ac8de440615, topicName=神经痛)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0d8213287489, createdName=贵阳, createdTime=Wed Apr 20 04:50:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580362, encodeId=da7b158036257, content=<a href='/topic/show?id=c026e05485f' target=_blank style='color:#2F92EE;'>#疱疹#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70548, encryptionId=c026e05485f, topicName=疱疹)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2dcf16628144, createdName=ms2694732865965676, createdTime=Wed Apr 20 04:50:00 CST 2016, time=2016-04-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79418, encodeId=7020e9418d3, content=学习了…, beContent=null, objectType=article, channel=null, level=null, likeNumber=233, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 00:49:00 CST 2016, time=2016-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79419, encodeId=4f0ae94197c, content=写的不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=163, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=240a1683959, createdName=李继凯, createdTime=Tue Apr 19 00:49:00 CST 2016, time=2016-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=79361, encodeId=2b8be936160, content=学习了,很好, beContent=null, objectType=article, channel=null, level=null, likeNumber=108, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=387d1660055, createdName=dhzzm, createdTime=Mon Apr 18 15:57:00 CST 2016, time=2016-04-18, status=1, ipAttribution=)]
    2016-04-18 dhzzm

    学习了,很好

    0