Phenotypes and treatment response: it's difficult to make predictions, especially about the future.
Phenotypes and treatment response: it's difficult to make predictions, especially about the future.
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表型和治疗反应：很难做出预测，尤其是对未来的预测。
DOI：
10.1097/j.pain.0000000000000771
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发表时间：
2017
期刊：
影响因子：
7.4
通讯作者：
Edwards,RobertR
中科院分区：
文献类型：
--
作者：
Dworkin,RobertH;Edwards,RobertR
25年前，Mitchell Max提出，可以通过靶向导致慢性神经性疼痛的特定病理生理机制来开发“更有效，毒性更小的治疗方法”。[14]这一建议是基于新出现的证据，即各种不同的机制导致不同患者的神经性疼痛，Max强调，基于机制的治疗方法的开发需要3项协调的研究工作：（1）疼痛机制和药物靶点的临床前研究;（2）开发与潜在疼痛机制相对应的患者分类;（3）临床试验旨在检查哪些患者亚组对特定治疗反应最好。14在过去的20年里，临床前研究的结果是理解急性和慢性疼痛机制的主要进展。然而，相当少的注意力已经致力于确定患者的疼痛机制，并发现有效的药物作用于这些机制。鉴于现有止痛药的疗效一般不高，耐受性往往存在问题，一个至关重要的研究重点是确定是否有患者群体在给予特定治疗时反应的可能性增加（或耐受性更好）。11，19这些努力包括对患者进行基因分型和表型的各种方法，这些方法有可能加速精确（即个性化）疼痛治疗的发展。8然而，重要的是要强调，治疗与患者的相互作用设定了治疗反应中基因型和表型差异的上限16，并且尚未确定现有疼痛治疗的这种变异性来源的大小。7然而，感觉表型已成为确定潜在疼痛机制的工作重点，从而有可能检查假设的基于机制的治疗的疗效。感觉表型包括体征或症状特征的识别，通常使用定量感觉测试（QST）和条件性疼痛调制来评估体征和患者报告的结果测量来评估症状。
Over 25 years ago, Mitchell Max proposed that “more effective, less toxic treatments” could be developed by targeting the specific pathophysiologic mechanisms that account for chronic neuropathic pain. 14 This suggestion was based on emerging evidence that a variety of distinct mechanisms contribute to neuropathic pain in different patients with different conditions, and Max emphasized that the development of mechanism-based treatments would require 3 coordinated research efforts:(1) preclinical studies of pain mechanisms and drug targets;(2) the development of classifications of patients that correspond to underlying pain mechanisms;(3) and clinical trials designed to examine which patient subgroups respond best to specific treatments. 14 In the past 2 decades, the results of preclinical research have been responsible for major advances in understanding the mechanisms of acute and chronic pain. However, considerably less attention has been devoted to identifying pain mechanisms in patients and discovering efficacious medications that act on those mechanisms. Given the generally modest efficacy and often problematic tolerability of existing pain medications, a critically important research focus involves determining whether there are groups of patients who have an increased likelihood of response (or better tolerability) when administered a specific treatment. 11, 19 Such efforts include various approaches to genotyping and phenotyping patients, which have the potential to accelerate the development of precision (ie, personalized) pain treatments. 8 It is important to emphasize, however, that treatment-by-patient interaction sets an upper bound on genotypic and phenotypic differences in treatment response16 and that the magnitude of this source of variability has not been determined for existing pain treatments. 7 Nevertheless, sensory phenotyping has become a focus of efforts to identify underlying pain mechanisms and thereby make it possible to examine the efficacy of hypothesized mechanism-based treatments. Sensory phenotyping involves the identification of profiles of signs or symptoms, often using quantitative sensory testing (QST) and conditioned pain modulation to evaluate signs and patient-reported outcome measures to assess symptoms.