title: Prostaglandin E2 and pain--an update.
abstract: 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.
authors.affiliation: Division of Pharmacology and Pathophysiology, School of Pharmacy, Kinki University, Higashi-Osaka 577–8502, Japan. kawabata@phar.kindai.ac.jp
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Kawabata
mesh_terms: D015746:Abdominal Pain / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000378:metabolism* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D006930:Hyperalgesia / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008881:Migraine Disorders / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D010148:Intractable Pain / Q000188:drug therapy; D011494:Protein Kinases / Q000378:metabolism*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000700:Analgesics; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D018078:Receptors, Prostaglandin E; D011494:Protein Kinases; D015232:Dinoprostone