Ceccarelli Ilaria, Fiorenzani Paolo, Pessina Federica, Pinassi Jessica, Aglianò Margherita, Miragliotta Vincenzo, Aloisi Anna Maria
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Front Neurosci. 2020 Aug 18;14:850. doi: 10.3389/fnins.2020.00850. eCollection 2020.
Cannabinoids help in pain treatment through their action on CB1 and CB2 receptors. β-caryophyllene (BCP), an ancient remedy to treat pain, is a sesquiterpene found in large amounts in the essential oils of various spice and food plants such as oregano, cinnamon, and black pepper. It binds to the CB2 receptor, acting as a full agonist. Sex differences in the BCP-induced analgesic effect were studied by exposing male and female rats to a persistent/repeated painful stimulation. To simulate treatment of a repeated inflammatory condition, after the first formalin injection (FT1; 50 μl, 2.5%), rats received BCP for 7 days at two dosages: 5 and 10 mg/kg dissolved in olive oil (OIL). The control group was treated with OIL for 7 days. On day 8, the formalin test was repeated (FT2) with a lower formalin concentration (50 μl, 1%). During the first and second formalin tests, pain-induced responses (licking, flexing, and paw jerk) and spontaneous behaviors were recorded and analyzed. In the FT1 (before the beginning of treatment with BCP), females displayed higher pain responses than did males in terms of flexing duration during the first part of the test (I phase and interphase), while during the second part (II phase early and late) males showed higher levels than did females in licking duration. In the FT2, the pain responses generally decreased in the BCP groups in a dose-dependent manner (i.e., greater effect of BCP10), with a more pronounced reduction in males than in females; moreover, the pain responses remained high in the OIL groups and in the female BCP5 group. In conclusion, long-term intake of BCP appears to be able to decrease pain behaviors in a model of repeated inflammatory pain in both sexes, but to a greater degree in males.
大麻素通过作用于CB1和CB2受体来帮助治疗疼痛。β-石竹烯（BCP）是一种古老的止痛药物，是一种倍半萜烯，大量存在于各种香料和食用植物（如牛至、肉桂和黑胡椒）的精油中。它与CB2受体结合，作为一种完全激动剂发挥作用。通过将雄性和雌性大鼠暴露于持续/重复的疼痛刺激下，研究了BCP诱导的镇痛作用中的性别差异。为了模拟对反复炎症状态的治疗，在首次注射福尔马林（FT1；50 μl，2.5%）后，大鼠以两种剂量接受BCP治疗7天：5和10 mg/kg溶解于橄榄油（OIL）中。对照组用橄榄油治疗7天。在第8天，用较低浓度的福尔马林（50 μl，1%）重复进行福尔马林试验（FT2）。在第一次和第二次福尔马林试验期间，记录并分析疼痛诱导的反应（舔舐、屈曲和爪部抽搐）以及自发行为。在FT1（开始用BCP治疗之前），在试验的第一部分（I期和间期），雌性在屈曲持续时间方面比雄性表现出更高的疼痛反应，而在第二部分（II期早期和晚期），雄性在舔舐持续时间方面比雌性表现出更高的水平。在FT2中，BCP组的疼痛反应通常以剂量依赖性方式降低（即，BCP10的效果更大），雄性的降低比雌性更明显；此外，OIL组和雌性BCP5组的疼痛反应仍然很高。总之，长期摄入BCP似乎能够降低两性反复炎症性疼痛模型中的疼痛行为，但在雄性中降低程度更大。
