Prostanoids and pain: unraveling mechanisms and revealing therapeutic targets.
Advances in our understanding of the synthesis, regulation and function of prostanoids have led to a new appreciation of their actions in health and disease. Prostanoid synthesis is essential for the generation of inflammatory pain and this depends not only on prostanoid production at the site of inflammation, but also on the actions of prostanoids synthesized within the central nervous system (CNS). Moreover, central prostanoid synthesis is controlled both by neural and humoral signals, the latter being a novel form of input to the CNS. Diverse compounds that act along the pathway of prostanoid synthesis and action, both in the periphery and in the CNS, might provide increased benefit for treating inflammatory pain hypersensitivity and its associated sickness syndrome, with a reduced risk of adverse effects.
Samad
Tarek A
TA
Neural Plasticity Research Group, Dept of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Sapirstein
Adam
A
Woolf
Clifford J
CJ
D016718:Arachidonic Acid / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000628:therapy; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000503:physiopathology; D059408:Pain Management; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D016718:Arachidonic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A