The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features

Gronwald, Carsten; Vegh, Vladimir; Hollmann, Markus W.; Hahnenkamp, Anke; Garaj, Vladimír; Hahnenkamp, Klaus

doi:10.1016/j.ejphar.2011.10.035

Cited by 15 publications

(7 citation statements)

References 22 publications

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“…() and Gronwald et al. () expressed human GluN1/GluN2A NMDA receptors in Xenopus oocytes and stimulated these with glutamate/glycine. Lidocaine inhibits the NMDA receptor in a dose‐dependent manner via an intracellular binding site.…”

Section: Resultsmentioning

confidence: 99%

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

Wal

Heuvel

Radema

et al. 2015

European Journal of Pain

108

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Section: Resultsmentioning

confidence: 99%

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

Wal

Heuvel

Radema

et al. 2015

European Journal of Pain

108

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“…Management of pain due to the activation of the NMDA receptor includes efforts to close it or prevent its activation. Medications that may close the NMDA receptor, at least partially, include opioid rotation, ketamine , methadone , lidocaine, and other local anesthetics as reported by a few case reports and anecdotes. Methadone is a racemic compound with dextro‐ and levo‐isomers ( dl ‐methadone).…”

Section: Intractable Vocs With Persistent Pain In Between Episodesmentioning

confidence: 99%

Pathophysiology and principles of management of the many faces of the acute vaso‐occlusive crisis in patients with sickle cell disease

Ballas

2014

European J of Haematology

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Effective management of sickle cell pain entails a thorough understanding of its pathophysiology and the pharmacogenomics of the opioids used to manage it. In recent years, there has been significant progress along these two lines. At the pathophysiologic level, there is evidence that the severity and frequency of painful stimuli modulate their transmission at the level of the dorsal horn of the spinal cord. This modulation is achieved via two channels: the a-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors. Initially, the AMPA channel controls the transmission of stimuli of mild-moderate severity. Once the AMPA channel reaches its limit of membrane depolarization, the NMDA channel is activated and facilitates the transmission of painful stimuli in a progressive fashion leading to central sensitization and glial activation. At the level of pharmacogenomics, the metabolism of each opioid is patient-specific. Glucuronidation is unique for the metabolism of morphine, hydromorphone, and oxymorphone. The metabolism of all other opioids requires specific Cytochrome P450 (CYP) isoenzymes. The activity of each isoenzyme and the activity of the metabolites of each opioid vary among patients depending on their genetic makeup and coexistent environmental factors such as the use of other medications that may enhance or inhibit the CYP isoenzyme activity. The clinical picture of sickle cell disease (SCD) in general and sickle cell anemia (SS) in particular has evolved significantly over the years. In the 1950s, 1960s, and 1970s, many patients died during childhood or young adulthood (1-3) and the knowledge of healthcare providers about sickle cell pain and its management were suboptimal. Since then, things have improved significantly but not totally. With the advent of newborn screening, penicillin/antibiotic prophylaxis, better vaccines, better antibiotics, safer blood transfusion, iron chelation therapy and hydroxyurea survival and the quality of life of patients with SCD improved (4, 5), and it is not unusual nowadays to have occasional patients with SCD who are 50-70 yr old. With increased longevity, however, a host of new phenomena appeared and the incidence of new complications of SCD became apparent and previously milder complications became more severe and more common. The acute vaso-occlusive crisis (VOC), for example, is no more characterized by the intermittent sudden onset and sudden offset only with pain-free periods in between recurrent VOCs; chronic pain syndromes have become more common and more severe requiring special treatments and interventions, neuropathic pain has been well documented in transgenic sickle cell mice, and most importantly numerous comorbidities emerged that complicate the already complex disease. There are at least 23 comorbid conditions reported in SCD (6). Despite these advances, management of acute sickle cell pain did not change much; it is still fixed at the level of type, amount, frequency, and

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“…Lidocaine limits peripheral and central sensitization. This antihyperalgesic effect is mainly the result of suppression of the neuro-inflammatory response to pain, blockade of neural transmission, inhibition of NMDA receptor and modulation of the glycinergic system [21, 26,27]. Low-dose lidocaine improves glycinergic signaling, and high dose inhibits it.…”

Section: Discussionmentioning

confidence: 99%

Lidocaine as an element of multimodal analgesic therapy in major spine surgical procedures in children: a prospective, randomized, double-blind study

et al. 2020

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Background Introducing the principles of multimodal analgesic therapy is necessary to provide appropriate comfort for the patient after surgery. The main objective of the study was evaluating the influence of perioperative intravenous (i.v.) lidocaine infusion on postoperative morphine requirements during the first 48 h postoperatively in children undergoing major spine surgery. Materials and methods Prospective, randomized, double-blind study: 41 children, qualified to multilevel spine surgery, were randomly divided into two treatment groups: lidocaine and placebo (control). The lidocaine group received lidocaine as a bolus of 1.5 mg/kg over 30 minutes, followed by a continuous infusion at 1 mg/kg/h to 6 hours after surgery. The protocol of perioperative management was identical for all patients. Measurements: morphine demand, intensity of postoperative pain (the Numerical Rating Scale), oral feeding initiation time, first attempts at assuming erect position, postoperative quality of life (the Acute Short-form /SF-12/ health survey). Results Patient data did not differ demographically. Compared to the control group, lidocaine treatment reduced the demand for morphine during the first 24h [95% CI 0.13 (0.11-0.28) mg/kg, p = 0.0122], 48h [95% CI 0.46 (0.22-0.52) mg/kg, p = 0.0299] after surgery and entire hospitalization [95% CI 0.58 (0.19-0.78) mg/kg, p = 0.04]; postoperative pain intensity; nutritional withdrawal period [introduction of liquid diet (p = 0.024) and solid diet (p = 0.012)], and accelerated the adoption of an upright position [sitting (p = 0.048); walking (p = 0.049)]. The SF-12 generic health survey did not differ between groups before operation, 2 months and 4 years after surgery. Conclusions Perioperative lidocaine administration, as a part of the applied analgesic therapy regimen, may decrease postoperative opioid demand and accelerates convalescence of children undergoing major surgery.

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The inhibitory potency of local anesthetics on NMDA receptor signalling depends on their structural features

Cited by 15 publications

References 22 publications

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain

Pathophysiology and principles of management of the many faces of the acute vaso‐occlusive crisis in patients with sickle cell disease

Lidocaine as an element of multimodal analgesic therapy in major spine surgical procedures in children: a prospective, randomized, double-blind study

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