Division of Pharmacology and Pathophysiology, School of Pharmacy, Kinki University, Higashi-Osaka 577–8502, Japan.
Biol Pharm Bull. 2011;34(8):1170-3. doi: 10.1248/bpb.34.1170.
Prostaglandin E(2) (PGE(2)), a cyclooxygenase (COX) product, is the best known lipid mediator that contributes to inflammatory pain. Nonsteroidal anti-inflammatory drugs (NSAIDs), inhibitors of COX-1 and/or COX-2, suppress inflammatory pain by reducing generation of prostanoids, mainly PGE(2), while they exhibit gastrointestinal, renal and cardiovascular toxicities. Selective inhibitors of microsomal PGE synthase-1 and subtype-selective antagonists of PGE(2) receptors, particularly EP(1) and EP(4), may be useful as analgesics with minimized side-effects. Protein kinase C (PKC) and PKA downstream of EP(1) and EP(4), respectively, sensitize/activate multiple molecules including transient receptor potential vanilloid-1 (TRPV1) channels, purinergic P2X3 receptors, and voltage-gated calcium or sodium channels in nociceptors, leading to hyperalgesia. PGE(2) is also implicated in neuropathic and visceral pain and in migraine. Thus, PGE(2) has a great impact on pain signals, and pharmacological intervention in upstream and downstream signals of PGE(2) may serve as novel therapeutic strategies for the treatment of intractable pain.
前列腺素 E（2）（PGE（2））是环氧化酶（COX）产物，是已知的参与炎症性疼痛的最佳脂质介质。非甾体抗炎药（NSAIDs）是 COX-1 和/或 COX-2 的抑制剂，通过减少前列腺素的产生（主要是 PGE（2））来抑制炎症性疼痛，而它们表现出胃肠道、肾脏和心血管毒性。微粒体前列腺素 E 合酶-1 的选择性抑制剂和 PGE（2）受体的亚型选择性拮抗剂，特别是 EP（1）和 EP（4），可能作为具有最小副作用的镇痛药有用。EP（1）和 EP（4）下游的蛋白激酶 C（PKC）和 PKA 分别使包括瞬时受体电位香草酸 1（TRPV1）通道、嘌呤能 P2X3 受体和伤害感受器中的电压门控钙或钠通道在内的多种分子敏化/激活，导致痛觉过敏。PGE（2）也与神经性疼痛和内脏疼痛以及偏头痛有关。因此，PGE（2）对疼痛信号有很大影响，针对 PGE（2）的上游和下游信号的药物干预可能成为治疗难治性疼痛的新治疗策略。
