Prostaglandin E2 and Pain—An Update
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TLDR
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.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.read more
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Yukihiko Sugimoto,Shuh Narumiya +1 more
TL;DR: Recent advances in PGE receptor research are reviewed, including studies on knock-out mice deficient in each EP subtype have defined PGE2 actions mediated by each subtype and identified the role eachEP subtype plays in various physiological and pathophysiological responses.
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