Department of Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Pain Management Center, Harvard Medical School, Brigham and Women's Hospital, Chestnut Hill, MA, USA.
Pain Physician. 2021 May;24(3):243-252.
Control of chronic pain and mainly the partial or complete loss of response to analgesics is a major unmet need. Multiple mechanisms underline the development of tolerance to analgesics in general and specifically to opioids. The autonomic nervous system (ANS) plays a role in the development of analgesic tolerance and chronobiology.
To review the mechanisms associated with the development of nonresponsiveness to analgesics.
Literature review.
The review is followed by a description of a new method for overcoming resistance and improving the response to analgesics.
Conducted a detailed review of the relevant studies describing the mechanisms that underlie tolerance to pain medications, and the potential roles of the ANS and chronobiology in the development of drug resistance.
The autonomic balance is reflected by heart rate variability, an example of a fundamental variability that characterizes biological systems. Chronotherapy, which is based on the circadian rhythm, can improve the efficacy and reduce the toxicity of chronic medications. In this article, we present the establishment of an individualized variability- and chronobiology-based therapy for overcoming the compensatory mechanisms associated with a loss of response to analgesics. We describe the premise of implementing personalized signatures associated with the ANS, and chronobiology, as well as with the pathophysiology of pain for establishing an adaptive model that could improve the efficacy of opioids, in a highly dynamic system.
The studies presented were selected based on their relevance to the subject.
The described variability-based system may ensure prolonged effects of analgesics while reducing the toxicity associated with increasing dosages.
慢性疼痛的控制，主要是对镇痛剂的部分或完全无反应，是一个主要的未满足的需求。多种机制导致了对镇痛剂的耐受性的发展，特别是对阿片类药物。自主神经系统（ANS）在镇痛剂耐受性和时间生物学的发展中起作用。
综述与镇痛剂无反应性发展相关的机制。
文献综述。
综述后面是一种克服耐药性和提高镇痛剂反应的新方法的描述。
对描述疼痛药物耐受性的潜在机制的相关研究进行了详细的综述，以及自主神经系统和时间生物学在耐药性发展中的潜在作用。
心率变异性反映了自主平衡，这是一个生物系统特征的基本可变性的例子。基于昼夜节律的时间治疗可以提高慢性药物的疗效，降低毒性。在本文中，我们提出了建立一种个体化的变异性和时间生物学为基础的治疗方法，以克服与镇痛剂反应丧失相关的代偿机制。我们描述了实施与自主神经系统、时间生物学以及疼痛病理生理学相关的个性化特征的前提，以及建立一个适应性模型，以改善阿片类药物的疗效，在一个高度动态的系统中。
所呈现的研究是根据其与主题的相关性选择的。
所描述的基于变异性的系统可以确保镇痛剂的长期效果，同时降低与增加剂量相关的毒性。
