Pharmacotechnology Documentation and Transfer Unit, Preclinical and Translational Pharmacology, Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy.
Regional Center for Serious Brain Injuries, S. Anna Institute, 88900 Crotone, Italy.
Molecules. 2022 Aug 5;27(15):4987. doi: 10.3390/molecules27154987.
Chronic pain is one of the most common causes of the need for clinical evaluation, acquiring more importance in the elderly with cognitive impairment. Reduced self-reporting capabilities cause unrelieved pain contributing to the development of agitation. Safe and effective pain treatment can afford the management of agitation without the serious increase in death risk associated with neuroleptics. To this aim, the essential oil of bergamot (BEO), proven by rigorous evidence to have strong preclinical anti-nociceptive and anti-allodynic properties, has been engineered (NanoBEO, patent EP 4003294) to allow randomized, double-blind, placebo-controlled trials (BRAINAID, NCT04321889). The present study: (1) assesses the analgesic effects of a single therapeutic dose of NanoBEO, as supplied by an airless dispenser for clinical translation, in models of inflammatory, neuropathic, and sensitization types of pain relevant to clinic; (2) provides a dose-response analysis of the efficacy of NanoBEO on scratching behavior, a typical behavioral disturbance occurring in dementia. A single therapeutic dose of NanoBEO confirms efficacy following thirty minutes pre-treatment with capsaicin and on the central sensitization phase induced by formalin. Moreover, it has an ID50 of 0.6312 mg and it is efficacious on static and dynamic mechanical allodynia. Altogether, the gathered results strengthen the potential of NanoBEO for clinical management of pain and agitation.
慢性疼痛是临床评估需求最常见的原因之一，在认知障碍的老年人中更为重要。自我报告能力下降导致疼痛未得到缓解，从而导致激越。安全有效的疼痛治疗可以在不增加与神经阻滞剂相关的严重死亡风险的情况下，管理激越。为此，经过严格证据证明具有强大的临床前镇痛和抗感觉过敏特性的佛手柑精油（BEO）已被设计（NanoBEO，专利 EP 4003294），以允许进行随机、双盲、安慰剂对照试验（BRAINAID，NCT04321889）。本研究：（1）评估了用于临床转化的无气分配器提供的单次治疗剂量的 NanoBEO 在与临床相关的炎症、神经病理性和致敏性疼痛模型中的镇痛作用；（2）分析了 NanoBEO 对抓挠行为的疗效的剂量反应，抓挠行为是痴呆症中发生的一种典型行为障碍。NanoBEO 的单次治疗剂量在辣椒素预处理 30 分钟后以及福尔马林诱导的中枢敏化阶段均证实有效。此外，它的 ID50 为 0.6312 mg，对静态和动态机械性感觉过敏均有效。综上所述，收集的结果增强了 NanoBEO 用于疼痛和激越的临床管理的潜力。
