Toloff Katelyn, Woodcock Eric A
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
Med Res Arch. 2022 Aug;10(8). doi: 10.18103/mra.v10i8.2955.
Opioid use disorder (OUD) is an epidemic in the United States. In the past 12 months alone, there have been 75,000+ deaths attributed to opioid overdose: more than any other year in American history. Current pharmacotherapies for the treatment of OUD effectively suppress opioid withdrawal symptoms, but long-term relapse rates remain unacceptably high. Novel treatments for OUD are desperately needed to curb this epidemic. One target that has received considerable recent interest is the neuroimmune system. The neuroimmune system is anchored by glial cells, i.e., microglia and astrocytes, but neuroimmune signaling is known to influence neurons, including altering neurotransmission, synapse formation, and ultimately, brain function. Preclinical studies have shown that experimental attenuation of pro-inflammatory neuroimmune signaling modulates opioid addiction processes, including opioid reward, tolerance, and withdrawal symptoms, which suggests potential therapeutic benefit in patients. Whereas the peripheral immune system in OUD patients has been studied for decades and is well-understood, little is known about the immune system in OUD patients or its viability as a treatment target. Herein, we review the literature describing relationships between opioid administration and the neuroimmune system, the influence of neuroimmune signaling on opioid addiction processes, and the therapeutic potential for targeting the neuroimmune system in OUD subjects using glial modulator medications.
阿片类药物使用障碍（OUD）在美国呈泛滥之势。仅在过去12个月里，就有超过7.5万人死于阿片类药物过量：这一数字超过了美国历史上的任何一年。目前用于治疗OUD的药物疗法能有效抑制阿片类药物戒断症状，但长期复发率仍高得令人难以接受。迫切需要新的OUD治疗方法来遏制这一泛滥情况。最近备受关注的一个靶点是神经免疫系统。神经免疫系统以神经胶质细胞为基础，即小胶质细胞和星形胶质细胞，但已知神经免疫信号会影响神经元，包括改变神经传递、突触形成，并最终影响脑功能。临床前研究表明，促炎性神经免疫信号的实验性减弱可调节阿片类药物成瘾过程，包括阿片类药物奖赏、耐受性和戒断症状，这表明对患者可能具有治疗益处。尽管对OUD患者的外周免疫系统已研究了数十年且已被充分了解，但对OUD患者的免疫系统及其作为治疗靶点的可行性却知之甚少。在此，我们综述了描述阿片类药物给药与神经免疫系统之间关系、神经免疫信号对阿片类药物成瘾过程的影响以及使用神经胶质调节剂药物靶向OUD患者神经免疫系统的治疗潜力的文献。
