Ketamine pain mechanism
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Ketamine Pain Mechanism
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Pain is communicated from the brain to other parts of the body by the CNS (Central Nervous System ) and nerve endings (Mayer , Mao , Holt Price , 7731-7736 ) The ligand-gated ion channels , also referred to as LGICs , or ionotropic receptors , are a group of intrinsic transmembrane ion channels that are opened in response to binding of a chemical messenger (Collingridge , Singer , 290-296 (Dickenson , 307-309 (Dickenson , Chapman , Green , 633-638 ) The ion channel is regulated by a neurotransmitter ligand that is very selective to one or [banner_entry_middle]
more ions like potassium , sodium , calcium , and chloride (Kandel , Schwartz , Jessell 178-180 ) Such receptors located at synapses converting the chemical signal to an electric signal in the post-synaptic cell (Connolly Wafford , 529-534 ) The NMDA receptor (N-methyl-D-aspartate ) is such an ionotropic receptor for glutamate (Dingledine , Borges , Bowie Traynelis , 7-61 (Lodge , Johnson , 81-86 (Meller , 435-436 ) By X-ray crystallography , the NMDA receptors have an heterodimer subunits , which are involved in the binding of agonists and antagonists like Ketamine (Hirota , Lambert , 441-444 ) This channel complex contributes to excitatory synaptic transmission at sites throughout the brain and the spinal cord , and is modulated by a number of endogenous and exogenous compounds (Rabben , Skljelbred , Oye , 1060-1066 ) NMDA receptors play a key role in a wide range of physiologic and pathologic processes (Hoffman , Coppejans , Vercauteren , Adriemsen , 240-242 (Klepstadt Maurset , Moberg , Oye , 513-518 (Coderre , Katz , Vaccarino , Melzack 259-285 ) Ketamine is primarily a non-competitive antagonist , which opens in response to binding of glutamate . This NMDA receptor mediates the reduction of pain effects of ketamine at low doses (Lofwall , Griffiths Mintzer , 439-449 ) Evidence for this is reinforced by the fact that naxolone , an opioid antagonist , does not reverse the analgesia . Studies also seem to indicate that ketamine is ‘use dependent ‘ meaning it only initiates its blocking action once a glutamate binds to the NMDA receptor (Sorensen , Bengtsson , Ahlner , Henriksson , Ekselius et al 1615-1621 ) At high level doses , ketamine has also been found to bind to opioid mu receptors and sigma receptors . Thus , loss of consciousness that occurs may be partially due to binding at the opioid mu and sigma receptors (Lonnqvist , Norton , 617-621 (Menigaux , Fletcher , Dupont , Guignard , Guirimand , et al . 129-135 (Koppert , Sittl , Scheuber , Alsheimer , Schmelz , 152-159 (Bushell , Endoh Simen , Ren , Bindokas , 55-64 Works Cited
Mayer DJ , Mao J , Holt J , Price DD . Cellular Mechanisms of Neuropathic Pain , Morphin Tolerance , and their Interactions . Proc . Natl Acac . Sci USA . 1999 , 96 (14 : 7731-7736
Collingridge G , Singer W . Excitatory Amino Acid Receptors and Synaptic Plasticity . Trends Pharmacol Sci . 1990 11 : 290-296
Dickenson AH . A cure for wind-up : NMDA receptor antagonists as potential analgesics . Trends Pharmacol Sci 1990 11 : 307-309
Dickenson AH , Chapman V and Green GM . The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord . Gen Pharmacol 1997 28 : 633-638
Kandel ER , Schwartz JH , Jessell TM . Principles of Neural Science , 4th ed . McGraw-Hill : New York (2000 , pp .178-180
Connolly CN , Wafford KA . The Cys-Loop Superfamily of Ligand-Gated Ion Channels – the… [banner_entry_footer]
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