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阿片类药物诱导的痛觉过敏与脊柱疼痛管理中的炎症衰老:基因导向多巴胺稳态的情况

Opioid-Induced Hyperalgesia and Inflammaging in the Management of Spine Pain: The Case for Genetically Directed Dopamine Homeostasis.

作者信息

Lewandrowski Kai-Uwe, Alvim Fiorelli Rossano Kepler, Schmidt Sergio, Sharafshah Alireza, Baron David, Gold Mark S, Thanos Panayotis K, Elman Igor, Bagchi Debasis, Bowirrat Abdalla, Pinhasov Albert, Lorio Morgan P, Blum Kenneth

机构信息

Department of Orthopedics, University of Arizona, Banner Medical Center, Tucson, Arizona, USA

Division Personalized Pain Research and Education, Center for Advanced Spine Care of Southern Arizona, Tucson, AZ, USA.

出版信息

Int J Spine Surg. 2025 Sep 2;19(4):459-484. doi: 10.14444/8756.

Abstract

BACKGROUND

The management of spine-related pain with narcotics, both before and after surgery, poses major challenges, including drug diversion, limited effectiveness, and worsening of pain symptoms over time. Chronic opioid use is associated with hypodopaminergia-induced hyperalgesia, whereby dopamine depletion increases pain sensitivity. Patients with inherently low dopaminergic function are particularly predisposed to hyperalgesia and reduced pain tolerance.

METHODS

An alternative therapeutic strategy centers on genetically guided pro-dopamine regulation, which aims to transmodulate dopaminergic signaling to mitigate hyperalgesia. Early identification of predisposition through genetic testing, combined with pharmacogenetic and pharmacogenomic monitoring, is proposed to optimize treatment approaches.

RESULTS

Pro-dopamine regulators have demonstrated promising results across 43 clinical studies, showing potential to reduce stress, craving, and relapse rates, while improving emotional well-being and attenuating pain sensitivity. These findings suggest that pro-dopamine regulation may serve as a viable frontline therapy for managing chronic pain and associated Reward Deficiency Syndrome behaviors, offering a significant reduction in the adverse effects commonly observed with chronic opioid therapy.

CONCLUSIONS

Given the limitations of dopaminergic blockade through chronic opioid agonist therapy, there is a critical need to reevaluate current pain management practices. The induction of dopamine homeostasis via pro-dopamine regulation represents a novel and potentially transformative strategy. Spine surgeons, pain specialists, and addiction medicine practitioners are urged to consider this approach as a promising alternative for improving long-term outcomes in patients suffering from chronic pain.

摘要

背景

脊柱相关疼痛在手术前后使用麻醉药品进行管理面临重大挑战,包括药物滥用、疗效有限以及随着时间推移疼痛症状恶化。长期使用阿片类药物与多巴胺能减退诱导的痛觉过敏有关,即多巴胺耗竭会增加疼痛敏感性。多巴胺能功能天生较低的患者尤其易患痛觉过敏且疼痛耐受性降低。

方法

一种替代治疗策略以基因引导的前多巴胺调节为核心,旨在调节多巴胺能信号传导以减轻痛觉过敏。建议通过基因检测早期识别易感性,并结合药物遗传学和药物基因组学监测来优化治疗方法。

结果

前多巴胺调节剂在43项临床研究中已显示出有前景的结果,表明其有潜力降低压力、渴望和复发率,同时改善情绪健康并减轻疼痛敏感性。这些发现表明,前多巴胺调节可能作为一种可行的一线疗法来管理慢性疼痛及相关的奖赏缺乏综合征行为,能显著减少慢性阿片类药物治疗中常见的不良反应。

结论

鉴于慢性阿片类激动剂疗法在多巴胺能阻滞方面的局限性,迫切需要重新评估当前的疼痛管理实践。通过前多巴胺调节诱导多巴胺稳态是一种新颖且可能具有变革性的策略。敦促脊柱外科医生、疼痛专家和成瘾医学从业者将这种方法视为改善慢性疼痛患者长期预后的一种有前景的替代方案。

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