Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments.

Graphical abstract

中文翻译：

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揭示慢性疼痛与滥用阿片类药物和大麻之间的联系

超过 5000 万美国人患有慢性疼痛，其中许多人没有得到足够的治疗，也没有通过服用阿片类药物和大麻等药物进行自我治疗来控制疼痛。研究表明，慢性疼痛和物质使用障碍 (SUD) 之间存在高度共病，并且这些疾病具有许多共同的神经生物学基础，包括多巴胺能传递不足。通常用于自我治疗的药物，如阿片类药物和大麻，可以缓解情绪、令人烦恼的疼痛成分以及负面情绪影响，这些影响会导致滥用并增加发展成药物滥用的风险。然而，慢性疼痛与 SUD 发生之间的因果关系尚未明确。在这篇综述中，我们通过概述临床证据并详细介绍疼痛与药物滥用之间的神经生物学机制，讨论了证实慢性疼痛是阿片类药物和大麻使用障碍发生的危险因素这一主张的证据。慢性疼痛与阿片类药物和大麻滥用之间的联系的核心是阿片类药物和大麻的多巴胺能传递低下以及中脑边缘通路中多巴胺信号的调节。此外，我们还讨论了卡帕阿片受体激活和神经炎症在多巴胺传递中的作用、它们对阿片类药物和大麻戒断的贡献，以及潜在的新疗法。

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