Department of Neurology, Klinikum Großhadern, Ludwig-Maximilians-University, D-81377 Munich, Germany.
BMC Neurol. 2011 Mar 31;11:43. doi: 10.1186/1471-2377-11-43.
Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics.
In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy.
Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies.
疼痛，一般而言，头痛，特别是以涉及疼痛处理的大脑区域的活动变化为特征。治疗的挑战是确定具有分子靶标的药物，这些药物恢复健康状态，从而导致有意义的疼痛缓解，甚至无疼痛。疼痛感知的不同方面，即感觉和情感成分，也解释了为什么没有单一的单一靶结构用于治疗疼痛的方法。大脑区域的网络（“疼痛矩阵”）参与疼痛感知和疼痛控制。疼痛系统的这种多样化解释了为什么可以使用广泛的分子不同物质来治疗不同的疼痛状态，以及为什么近年来越来越多的研究描述了精确的多靶组合疗法与单药治疗相比具有更高的疗效。
本文讨论了几种固定剂量组合在治疗头痛方面的可用文献，并讨论了支持联合治疗在疼痛治疗中的作用的证据，特别是在头痛治疗中。多靶组合背后的科学依据是，单独成分无法达到的治疗益处，并且组合中的单个物质共同作用，具有相加或甚至相乘的效果，并共同作用以实现所需治疗效果的完整性。以乙酰水杨酸（ASA）、对乙酰氨基酚（acetaminophen）和咖啡因的固定剂量组合为例进行了详细审查。使用这种固定组合的主要优点是，活性成分作用于不同但明显的分子靶标，因此能够作用于比大多数单一镇痛药更多的涉及疼痛的信号级联，而不会给治疗增加更多的副作用。
像联合镇痛药这样的多靶治疗方法拓宽了治疗选择范围，使治疗效果完整，并使医生（在自我用药时，包括非处方药物，患者自己）能够根据患者的特定需求定制治疗方案。有大量的临床证据表明，这种多成分治疗比单成分治疗更有效。
