Trofimovitch Diana, Baumrucker Steven J
1 Department of Internal Medicine, East Tennessee State University James H Quillen College of Medicine, Johnson City, TN, USA.
2 Hospice and Palliative Medicine, Ballad Health System, Kingsport, TN, USA.
Am J Hosp Palliat Care. 2019 Oct;36(10):907-912. doi: 10.1177/1049909119838974. Epub 2019 Mar 27.
Pain can have a devastating effect on the quality of life of patients in palliative medicine. Thus far, majority of research has been centered on opioid-based pain management, with a limited empirical evidence for the use of nonopioid medications in palliative care. However, opioid and nonopioid medications such as nonsteroidal anti-inflammatory drugs have their limitations in the clinical use due to risk of adverse effects, therefore, there is a need for more research to be directed to finding an alternative approach to pain management in comfort care setting. The purpose of this article is to discuss a potential new drug that would adequately alleviate pain and enhance quality of life without significant risks of adverse effects that would limit its use. Naltrexone is a reversible competitive antagonist at μ-opioid and κ-opioid receptors, which when used at standard doses of 50 to 150 mg was initially intended for use in opioid and alcohol use disorders. However, it was discovered that its use in low doses follows alternate pharmacodynamic pathways with various effects. When used in doses of 1 to 5 mg it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation. It binds to Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory cytokines, therefore reducing inflammatory response. Its other mode of action involves transient opioid receptor blockade ensuing from low-dose use which upregulates opioid signaling resulting in increased levels of endogenous opioid production, known as opioid rebound effect. Low dose naltrexone has gained popularity as an off-label treatment of several autoimmune diseases including multiple sclerosis and inflammatory bowel disease, as well as chronic pain disorders including fibromyalgia, complex regional pain syndrome, and diabetic neuropathy. Low-dose naltrexone (LDN) may also have utility in improving mood disorders and the potential to enhance the quality of life. This article will therefore propose the potential off-label use of LDN in management of nonmalignant pain in the palliative medicine setting.
疼痛会对姑息治疗患者的生活质量产生毁灭性影响。到目前为止，大多数研究都集中在基于阿片类药物的疼痛管理上，而在姑息治疗中使用非阿片类药物的经验证据有限。然而，阿片类药物和非阿片类药物（如非甾体抗炎药）在临床使用中由于存在不良反应风险而有其局限性，因此，需要开展更多研究，以找到在舒适护理环境中进行疼痛管理的替代方法。本文的目的是讨论一种潜在的新药，它能充分缓解疼痛并提高生活质量，而不会有严重不良反应风险限制其使用。纳曲酮是μ-阿片受体和κ-阿片受体的可逆竞争性拮抗剂，最初以50至150毫克的标准剂量使用时，旨在用于阿片类药物和酒精使用障碍。然而，人们发现低剂量使用时它会遵循不同的药效学途径并产生各种效果。当以1至5毫克的剂量使用时，它作为一种神经胶质调节剂，通过抑制小胶质细胞活化发挥神经保护作用。它与Toll样受体4结合并作为拮抗剂起作用，从而抑制最终导致促炎细胞因子产生的下游细胞信号通路，进而减轻炎症反应。它的另一种作用方式涉及低剂量使用导致的短暂阿片受体阻断，这会上调阿片信号传导，导致内源性阿片产生水平增加，即所谓的阿片类药物反弹效应。低剂量纳曲酮作为几种自身免疫性疾病（包括多发性硬化症和炎症性肠病）以及慢性疼痛疾病（包括纤维肌痛、复杂性区域疼痛综合征和糖尿病性神经病变）的非标签治疗方法已受到欢迎。低剂量纳曲酮（LDN）在改善情绪障碍方面可能也有用处，并有提高生活质量的潜力。因此，本文将提出LDN在姑息医学环境中用于管理非恶性疼痛的潜在非标签用途。
