Wilson-Poe Adrianne R, Wiese Beth, Kibaly Cherkaouia, Lueptow Lindsay, Garcia Jeniffer, Anand Preeti, Cahill Catherine, Morón Jose A
Department of Neurobiology, Legacy Research Institute, Portland, OR, USA.
Departments of Anesthesiology, Neuroscience and Psychiatry, Washington University in St. Louis, St. Louis, MO, USA.
Pain Rep. 2021 Mar 5;6(1):e897. doi: 10.1097/PR9.0000000000000897. eCollection 2021 Jan-Feb.
The periaqueductal gray (PAG) mediates the antinociceptive properties of analgesics, including opioids and cannabinoids. Administration of either opioids or cannabinoids into the PAG induces antinociception. However, most studies characterizing the antinociceptive properties of cannabinoids in the PAG have been conducted in naive animals. Few studies have reported on the role of CB1 receptors in the PAG during conditions which would prompt the administration of analgesics, namely, during pain states.
To examine inflammatory pain-induced changes in CB1 receptor expression and function in the midbrain periaqueductal gray.
In this study, we used the Complete Freund Adjuvant model to characterize CB1 receptor expression and G-protein coupling during persistent inflammatory pain.
Inflammatory pain induced an upregulation in the expression of synaptic CB1 receptors in the PAG. Despite this pain-induced change in CB1 expression, there was no corresponding upregulation of CB1 mRNA after the induction of inflammatory pain, suggesting a pain-induced recruitment of CB1 receptors to the synaptic sites within PAG neurons or increased coupling efficiency between the receptor and effector systems. Inflammatory pain also enhanced ventrolateral PAG CB1 receptor activity, as there was an increase in CP55,940-stimulated G-protein activation compared with pain-naïve control animals.
These findings complement a growing body of evidence which demonstrate pain-induced changes in brain regions that are responsible for both the analgesic and rewarding properties of analgesic pharmacotherapies. Because much of our understanding of the pharmacology of cannabinoids is based on studies which use largely pain-naïve male animals, this work fills in important gaps in the knowledge base by incorporating pain-induced adaptations and cannabinoid pharmacology in females.
导水管周围灰质（PAG）介导包括阿片类药物和大麻素在内的镇痛药的抗伤害感受特性。将阿片类药物或大麻素注入PAG均可诱导抗伤害感受。然而，大多数关于PAG中大麻素抗伤害感受特性的研究是在未接触过相关药物的动物中进行的。很少有研究报道在促使使用镇痛药的情况下，即疼痛状态下，PAG中CB1受体的作用。
研究炎症性疼痛引起的中脑导水管周围灰质中CB1受体表达和功能的变化。
在本研究中，我们使用完全弗氏佐剂模型来表征持续性炎症性疼痛期间CB1受体的表达和G蛋白偶联。
炎症性疼痛诱导PAG中突触CB1受体表达上调。尽管炎症性疼痛引起了CB1表达的这种变化，但炎症性疼痛诱导后CB1 mRNA并没有相应上调，这表明炎症性疼痛诱导CB1受体募集到PAG神经元内的突触部位，或受体与效应系统之间的偶联效率增加。炎症性疼痛还增强了腹外侧PAG的CB1受体活性，因为与未接触过疼痛的对照动物相比，CP55,940刺激的G蛋白激活增加。
这些发现补充了越来越多的证据，这些证据表明疼痛会引起负责镇痛药物治疗的镇痛和奖赏特性的脑区发生变化。由于我们对大麻素药理学的大部分理解是基于主要使用未接触过疼痛的雄性动物的研究，这项工作通过纳入疼痛诱导的适应性变化和雌性动物中的大麻素药理学，填补了知识库中的重要空白。
