Matches in SemOpenAlex for { <https://semopenalex.org/work/W2025109356> ?p ?o ?g. }
- W2025109356 endingPage "189" @default.
- W2025109356 startingPage "173" @default.
- W2025109356 abstract "The lifetime incidence of chronic pain in Western populations is almost 50%, but current pharmacological treatments are poorly tolerated and ineffective against some types of pain, giving rise to a demand for new analgesic drugs. The primary symptoms of chronic pain are allodynia, hyperalgesia and spontaneous pain, all of which indicate a high level of excitability in central pain processing systems. Recent basic research has identified a bewildering number of molecules as actual or putative mediators of spinal hyperexcitability, and the main thrust of the present article is that antagonists for these molecules should provide new antihyperalgesic or analgesic treatments. Ionotropic glutamate receptors (particularly N-methyl-D-aspartate [NMDA], but including other calcium-permeable receptors), in conjunction with voltage-gated calcium channels, permit ingress of calcium ions into spinal dorsal horn neurones. In addition, group I metabotropic glutamate (mGlu) and tachykinin NK1 and NK3 receptors give rise to release of calcium from intracellular stores. In theory, antagonists for any of these receptors ought to be antihyperalgesic, but recent experience in clinical trials with NK1 receptor blockers has been disappointing. More encouragingly, non-selective antagonists for glutamate NMDA receptors are effective in all types of chronic pain in humans, albeit with side effects that are unacceptable. The recognition that NMDA receptors exist in multiple subtypes, and that the NR2B subtype is found (among only a few other sites) in the superficial dorsal horn of the spinal cord in rat, suggests that selective antagonists for these receptors may offer analgesia without the attendant problems of non-selective drugs. Selective antagonists for other calcium-permeable glutamate receptors, mGlu group I, NK3 and CGRP1 receptors may also have a future as antihyperalgesic agents, but all are at a very early stage of development. At present, the best hope for a powerful broad-spectrum antihyperalgesic lies with the NMDA receptor subtypes." @default.
- W2025109356 created "2016-06-24" @default.
- W2025109356 creator A5066469575 @default.
- W2025109356 date "2000-04-01" @default.
- W2025109356 modified "2023-10-18" @default.
- W2025109356 title "Synaptic mechanisms in nociception: emerging targets for centrally-acting analgesics" @default.
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