Department of Anesthesiology and Pain Medicine, Chung-Ang University College of Medicine, 84 Heukseok-ro, Dongjak-gu, Seoul, 06911, Republic of Korea.
Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
BMC Complement Med Ther. 2022 Jan 11;22(1):12. doi: 10.1186/s12906-021-03491-z.
Rubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs.
In adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 μg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction.
The iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups.
Immature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.
悬钩子，也被称为黑莓，含有几种生物活性成分，其取决于果实的成熟度。本研究的目的是评估未成熟悬钩子提取物（iROE）对酸诱导性痛觉过敏的疗效，探讨其涉及的机制，并比较未成熟和成熟 ROE 的抗痛觉过敏作用。
在成年雄性 Sprague-Dawley 大鼠中，通过向一侧腓肠肌注射两次酸性盐水来诱导慢性肌肉疼痛。为了评估剂量反应，在痛觉过敏发展后，大鼠经腹腔注射 0.9%生理盐水或 iROE（10、30、100 或 300mg/kg）。为了评估 iROE 诱导的镇痛作用的机制，在痛觉过敏发展后 24 小时，大鼠经腹腔注射生理盐水、育亨宾 2mg/kg、右美托咪定 50μg/kg、哌唑嗪 1mg/kg、阿托品 5mg/kg、美卡拉明 1mg/kg 或纳洛酮 5mg/kg，然后给予 iROE 300mg/kg。为了比较未成熟与成熟 ROE，在痛觉过敏发展后，大鼠经腹腔注射成熟 ROE 300mg/kg 和未成熟 ROE 300mg/kg。在所有实验中，在第一次酸性盐水注射前、第二次注射后 24 小时以及药物给药后各个时间点，使用 von Frey 细丝评估机械撤回避触阈值（MWT）。使用多变量方差分析（MANOVA）和线性混合效应模型（LMEM）分析数据。我们使用方差分析和 Bonferroni 校正比较每个时间点的 MWT。
与对照组、iROE 30mg/kg 组和 iROE 100mg/kg 组相比，iROE 300mg/kg 注射可显著增加同侧和对侧的 MWT。与单独使用 iROE 相比，iROE 注射与育亨宾、美卡拉明或纳洛酮一起可显著降低 MWT，而与右美托咪定一起可显著增加 MWT。根据 MANOVA，未成熟和成熟 ROE 的作用没有显著差异；然而，LMEM 显示两组之间存在显著差异。
未成熟的悬钩子对酸诱导的慢性肌肉疼痛具有抗痛觉过敏活性，其可能通过α-肾上腺素能、烟碱型胆碱能和阿片受体介导。与成熟 ROE 相比，iROE 显示出更好的镇痛效果倾向。
