Central and peripheral roles of prostaglandins in pain and their interactions with novel neuropeptides nociceptin and nocistatin.
While acute pain has a fundamental role to operate a protective system, chronic pain associated with inflammation and nerve injury often outlasts its biological usefulness. Therefore, there has recently been great interest in the neurochemical mechanisms of hyperalgesia to noxious stimuli and tactile pain (allodynia) to innocuous stimuli with a hope to relieve persistent, intractable pain. Over several decades non-steroidal anti-inflammatory drugs and opioids have been employed for clinical management of pain. The introduction of molecular biology to pain research has enabled us to describe the mechanism of pain at the molecular level and to develop analgesics with selectivity for targets and with less adverse effects. This review focuses on current knowledge concerning mechanisms and pathways for pain induced by prostaglandins and their interactions with novel neuropeptides nociceptin/orphanin FQ and nocistatin derived from the same opioid precursor protein.
Ito
S
S
Department of Medical Chemistry, Kansai Medical University, 10-15 Fumizono, Moriguchi 570-8506, Japan. ito@takii.kmu.ac.jp
Okuda-Ashitaka
E
E
Minami
T
T
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001095:Arachidonic Acids / Q000378:metabolism; D001921:Brain / Q000503:physiopathology; D002417:Cattle; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004357:Drug Synergism; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D008954:Models, Biological; D009437:Neuralgia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity; D009569:Nitric Oxide / Q000502:physiology; D009619:Nociceptors / Q000502:physiology; D018847:Opioid Peptides / Q000502:physiology*; D010146:Pain / Q000145:classification / Q000378:metabolism / Q000503:physiopathology*; D010525:Peripheral Nerves / Q000503:physiopathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000503:physiopathology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000097629:Nociceptin
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D051545:Cyclooxygenase 1; D016861:Cyclooxygenase Inhibitors; D018698:Glutamic Acid; D007527:Isoenzymes; D008565:Membrane Proteins; D009569:Nitric Oxide; D018847:Opioid Peptides; D011451:Prostaglandin-Endoperoxide Synthases; D011453:Prostaglandins; D011498:Protein Precursors; D013930:Thromboxane-A Synthase; D000097629:Nociceptin; C111148:nocistatin; C496511:PTGS1 protein, human; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat