Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, 1996835113 Tehran, Iran.
Neurochem Res. 2012 Apr;37(4):778-85. doi: 10.1007/s11064-011-0672-2. Epub 2011 Dec 27.
Most of the modulating effects of cannabinoids on pain are through putative cannabinoid CB1 and CB2 receptors. However, the involvement of other receptors is also suggested. Cannabinoid compounds with analgesic activity such as palmitoylethanolamide (PEA) show low affinity to CB1 and CB2 receptors, yet selectively activate GPR55 receptors. The objective of the present study was to evaluate the possible role of spinal CB1 and GPR55 receptors on antinociceptive activity of PEA in formalin test as well as in the spinal expression of IL1-β in rat. Intrathecal (i.t.) administration of PEA (1, 10 μg) significantly decreased both pain-related scores in formalin test and IL1-β expression in rat spinal cord. Pretreatment of rats with low doses of CB1 receptor antagonist/GPR55 receptor agonist AM251 (10, 100 ng; i.t.), did not attenuated the effect of PEA, yet even significantly increased the effect of PEA on IL1-β expression in rat spinal cord. Interestingly, i.t. administration of low doses of AM251 per se significantly decreased both pain related behavior and spinal IL1-β expression in formalin test. These findings suggest the possible involvement of receptors other than CB1 receptors in spinal pain pathways, such as GPR55, in pain modulating activity of cannabinoids.
大麻素对疼痛的大多数调节作用是通过假定的大麻素 CB1 和 CB2 受体实现的。然而，其他受体的参与也被提出。具有镇痛活性的大麻素化合物，如棕榈酰乙醇酰胺 (PEA)，对 CB1 和 CB2 受体的亲和力低，但选择性地激活 GPR55 受体。本研究的目的是评估脊髓 CB1 和 GPR55 受体在 PEA 对福尔马林试验中的镇痛活性以及大鼠脊髓中 IL1-β 表达中的可能作用。鞘内（i.t.）给予 PEA（1、10μg）可显著降低福尔马林试验中的疼痛相关评分和大鼠脊髓中 IL1-β 的表达。用低剂量 CB1 受体拮抗剂/GPR55 受体激动剂 AM251（10、100ng；i.t.）预处理大鼠，不能减弱 PEA 的作用，反而显著增加 PEA 对大鼠脊髓中 IL1-β 表达的作用。有趣的是，鞘内给予低剂量的 AM251 本身就显著降低了福尔马林试验中与疼痛相关的行为和脊髓中 IL1-β 的表达。这些发现表明，除了 CB1 受体以外，其他受体（如 GPR55）可能参与了大麻素在脊髓疼痛通路中的疼痛调节作用。
