Bordini Emilia C, Bordini Carlos A, Woldeamanuel Yohannes W, Rapoport Alan M
Ribeirão Medical School University Hospital, Ribeirão Preto, Brazil.
Clinica Neurológica Batatais, Batatais, Brazil.
Headache. 2016 Feb;56(2):422-35. doi: 10.1111/head.12771. Epub 2016 Feb 8.
The relationship between indomethacin (IMC) and headache treatment has long intrigued clinicians and clinical researchers in Headache Medicine. Why is it efficacious in many types of headache disorders when other medications are not, and what is the mechanism behind its efficacy? IMC and headache related topics that have been explored in detail in the literature include IMC-responsive headache disorders ("traditional"), pharmacology of IMC, symptomatic headaches responsive to IMC, "novel" headache conditions that respond, cluster headache and IMC, IMC provoking headache, the issue about" absolute" and "non-absolute" effect of IMC on headache disorders, and the morphing trigeminal autonomic cephalalgias (TACs).
A PubMed/MEDLINE search was used for Clinical Studies Categories and Systematic Reviews on the PubMed Clinical Queries. The search details were "indomethacin" AND "headache" spanning all previous years until February 1, 2015. Methods were in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Articles were excluded if IMC had not been used to treat headache disorders in adults, if the article concerned IMC-responsive headaches but made no reference to the use of IMC, and articles not addressing the above mentioned topics.
The "velocity" of publications on IMC and headache seems to be decreasing, particularly on the use of IMC for the treatment of TACs. The science behind the understanding of the putative mechanisms of IMC's action on headache has moved forward, but the answer to why it works better than other nonsteroidal anti-inflammatory drugs has been elusive. There are case reports of other rare headache disorders that may be responsive to IMC. The dosages of IMC used as a tool for detecting IMC responsive disorders vary according to different centers of investigation. In many circumstances, headache disorders similar to "primary" IMC-responsive disorders are actually symptomatic disorders. Cluster headache as an IMC-resistant headache disorder may not be as absolute as once thought. Sometimes, IMC has been found to provoke headache; differentiating IMC-provoked headache from IMC-resistant headache can make headache diagnosis and management difficult. As for the "absolute" responsiveness of IMC, it is possible that using higher dosages leads to higher sensitivity, probably at the expense of decreased specificity. There are many reports about the occurrence of two or more IMC-responsive disorders (latu sensu) in the same patient, which may be coincidental.
消炎痛（IMC）与头痛治疗之间的关系长期以来一直吸引着头痛医学领域的临床医生和临床研究人员。为何在其他药物无效时，它对多种类型的头痛疾病有效，其疗效背后的机制是什么？文献中已详细探讨的与IMC和头痛相关的主题包括对IMC有反应的头痛疾病（“传统型”）、IMC的药理学、对IMC有反应的症状性头痛、有反应的“新型”头痛病症、丛集性头痛与IMC、IMC诱发的头痛、IMC对头痛疾病的“绝对”和“非绝对”作用问题，以及变形性三叉自主神经性头痛（TACs）。
使用PubMed/MEDLINE在PubMed临床查询中的临床研究类别和系统评价进行检索。检索详情为“消炎痛”和“头痛”，涵盖截至2015年2月1日之前的所有年份。方法符合系统评价和Meta分析的首选报告项目指南。
如果文章未使用IMC治疗成人头痛疾病、文章涉及对IMC有反应的头痛但未提及IMC的使用，以及文章未涉及上述主题，则将其排除。
关于IMC和头痛的出版物“速度”似乎在下降，特别是关于IMC用于治疗TACs方面。对IMC作用于头痛的假定机制的理解背后的科学已经取得进展，但为何它比其他非甾体抗炎药效果更好的答案仍然难以捉摸。有其他罕见头痛疾病可能对IMC有反应的病例报告。用作检测对IMC有反应的疾病的工具时，使用的IMC剂量因不同的研究中心而异。在许多情况下，类似于“原发性”对IMC有反应的疾病的头痛疾病实际上是症状性疾病。丛集性头痛作为一种对IMC耐药的头痛疾病，可能并不像曾经认为的那样绝对。有时，发现IMC会诱发头痛；区分IMC诱发的头痛和对IMC耐药的头痛可能会使头痛的诊断和管理变得困难。至于IMC的“绝对”反应性，使用更高剂量可能会导致更高的敏感性，但可能是以降低特异性为代价。有许多关于同一患者出现两种或更多种对IMC有反应的疾病（广义）的报告，这可能是巧合。
