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Ketamine Use in Pain Management
Published in Sahar Swidan, Matthew Bennett, Advanced Therapeutics in Pain Medicine, 2020
Sahar Swidan, Charles E. Schultz
Ketamine is an N-methyl-d-aspartate (NMDA) non-competitive receptor antagonist that acts as an analgesic agent and has notable use in anesthesia, psychiatry, and pain management, among other disease states. N-methyl-d-aspartate amplifies pain signals, the development of central sensitization, and opioid tolerance.1 The NMDA receptor is integral in learning, memory, and synaptic plasticity.
Antiinflammatory Actions of VIP in the Lungs and Airways
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
Glutamate and related agonists, acting via glutamate NMDA receptors, form the major excitatory transmitter system in the mammalian brain (12). There is strong evidence that NMDA receptors, by promoting excessive entry of Ca2+ into neurons, play an important role in the neuronal damage that follows head injury, strokes, and epileptic seizures, and are associated with degenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (13). We recently presented evidence that NMDA receptors exist in the lung, and that their activation can trigger acute edematous lung injury (10,11). As in NMDA toxicity to central neurons, pulmonary excitotoxicity was associated with stimulation of nitric oxide (NO) synthesis, and could be attenuated by inhibition of this synthesis, as well as by NMDA receptor antagonists (10,11) (Fig. 2). The injury was also prevented by VIP (Fig. 2), apparently through inhibition of a key neurotoxic action of NO (see below; 11).
Neurotransmitters and Receptors, Ion Channels, G Proteins and Second Messengers
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The NMDA receptor is the most important glutamate receptor. It has four subunits. The central pore is blocked by magnesium and is activated by NMDA. Partial depolarization of the cell membrane is required to remove the Mg++ plug, resulting in the influx of Ca++ ions (Figure 3.7). The NMDA receptor has a role in learning and memory, central sensitization and wind-up or plasticity.
Neural Plasticity in the Ventral Tegmental Area, Aversive Motivation during Drug Withdrawal and Hallucinogenic Therapy
Published in Journal of Psychoactive Drugs, 2023
Hector Vargas-Perez, Taryn Elizabeth Grieder, Derek van der Kooy
Another possible route of action of 5-HT2A receptors is the long-term regulation of the expression of NMDA-like glutamate receptors (Zhong, Yuen, and Yan 2008). NMDA receptors are directly related to learning, particularly to the production and maintenance of potentiated glutamatergic signaling. Blockade of NMDA receptors with selective antagonists, such as ketamine, produces a relief of depressive symptoms almost instantaneously after their administration (Lapidus, Soleimani, and Murrough 2013; Niciu et al. 2014). However, because the regulation of the NMDA receptor is at the synaptic level, its therapeutic effects are generally short-term (around a week), and at best a couple of months (Lapidus, Soleimani, and Murrough 2013; Niciu et al. 2014). On the other hand, the long-term effects (more than 6 months (Griffiths et al. 2011)) of the action of agonists at 5-HT2A receptors could be due to a modification in the genetic transcription of glutamatergic NMDA receptors (Yuen et al. 2008), however this hypothesis needs to be corroborated experimentally.
Limbic encephalitis in a patient with systemic lupus erythematosus successfully treated with high-dose glucocorticoids and intravenous cyclophosphamide therapy: the potential pathogenicity of anti-glutamate receptor antibodies
Published in Modern Rheumatology Case Reports, 2021
Haruka Tsuchiya, Yukiko Iwasaki, Hirofumi Shoda, Yukitoshi Takahashi, Keishi Fujio
GluR is the receptor for glutamic acid, a stimulatory neurotransmitter, which is widely distributed in the central nervous system. GluR is classified into two types: the ionotropic and metabolic forms, and the former is subclassified pharmacologically into the N-methyl-D-aspartate (NMDA) and non-NMDA types. There are 18 subunits that comprise the ionotropic form, and each subunit is named according to the mouse (i.e. GluR α1-4, β1-3, γ1-2, ε1-4, ζ1, χ1-2 and δ1-2) or rat (i.e. GluR1-7, KA1-2, NR2A-2D, NR1, NR3A-3B and δ1-2) genes. The NMDA receptor consists of three or four subunits: an essential NR1 subunit and a subunit of NR2 or NR3. As the number of NMDA receptors is high in the corpus amygdaloideum, hypothalamus, cerebellum and hipoccampus, calcium entry through the NMDA receptor has been suggested to be related to the formation of learning and memory as well as controlling mood and behaviour [4].
Optimizing non-opioid pain control after implant-based breast reconstruction: a review of the literature and proposed pain control algorithm
Published in Journal of Plastic Surgery and Hand Surgery, 2020
Jeremie D. Oliver, Rebecca Knackstedt, James Gatherwright
A number of pharmacological protocols have been introduced into surgical pain control pathways in an effort to decrease narcotic dependence in patients recovering from surgery. Among these, ketamine is a dissociative agent that acts on the NMDA receptor. It has been shown to have questionable efficacy in improving postoperative pain following mastectomy when used alone but has been supported with positive outcomes in combination with local and regional anesthetic nerve blocks [40]. There has been promising data compiled in the literature of other surgical specialties on the positive effects of perioperative ketorolac. A meta-analysis of 13 randomized control trials (RCTs) in a diverse group of surgical patients found that perioperative ketorolac administration significantly reduced postoperative pain and opioid consumption, although this analysis did not account for hematoma incidence between groups [41].