scholarly journals Intranasal Application of Xenon Reduces Opioid Requirement and Postoperative Pain in Patients Undergoing Major Abdominal Surgery

2011 ◽  
Vol 115 (2) ◽  
pp. 398-407 ◽  
Author(s):  
Thorsten Frederik Holsträter ◽  
Michael Georgieff ◽  
Karl Josef Föhr ◽  
Werner Klingler ◽  
Miriam Elisabeth Uhl ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Postoperative Pain ◽  
Central Sensitization ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Study ◽  
Opioid Tolerance ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Intranasal Application

Background Both central sensitization after peripheral tissue injury and the development of opioid tolerance involve activation of N-methyl-D-aspartate (NMDA) receptors. At subanesthetic doses the NMDA receptor antagonist xenon suppresses pain-evoked sensitization of pain-processing areas in the central nervous system. Although numerous studies describe the effect of NMDA receptor antagonists on postoperative pain, clinical studies elucidating their intraoperative analgesic potency when applied in a low dosage are still largely missing. Methods To analyze the analgesic effect of low-dose xenon using new application methods, the authors tested nasally applied xenon as an add-on treatment for analgesia in 40 patients undergoing abdominal hysterectomy. Within a randomized double-blind placebo-controlled study design, intraoperative and postoperative requirement of opioids as well as postoperative subjective experiences of pain were measured as primary outcome variables. Results Intranasal application of xenon significantly reduced intraoperative opioid requirement (mean difference [MD] -2.0 μg/min; 95% CI [CI95]-0.53 to -3.51, Bonferroni correction adjusted P value [pcorr]= 0.028) without relevant side effects and significantly reduced postoperative pain (MD -1.34 points on an 11-point rating scale; CI95 -0.60 to -2.09, pcorr = 0.002). However, postoperative morphine consumption (MD -8.8 μg/min; CI95 1.2 to -18.8, pcorr = 0.24) was not significantly reduced in this study. Conclusions Low-dose xenon significantly reduces intraoperative analgesic use and postoperative pain perception. Because NMDA receptor antagonists suppress central sensitization, prevent the development of opioid tolerance, and reduce postoperative pain, the intraoperative usage of NMDA receptor antagonists such as xenon is suggested to improve effectiveness of pain management within a concept of multimodal analgesia.

Postinjury Pain Hypersensitivity and NMDA Receptor Antagonists

2018 ◽  
pp. 189-192
Keyword(s):  
Pain Management ◽  
Nmda Receptor ◽  
Central Sensitization ◽  
Receptor Activation ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Primary Afferent ◽  
Pain Hypersensitivity ◽  
Pain Pathways ◽  
Nmda Receptor Activation

This case focuses on pain hypersensitivity by asking the question: Are primary afferent-induced hypersensitivity states dependent on the activation of N-methyl-d-aspartate (NMDA) receptors, and is windup (perceived increase in pain intensity with a repeatedly delivered stimulus) a possible trigger for the production of central hypersensitivity? This study demonstrated that the induction and maintenance of central sensitization are dependent on NMDA receptor activation. NMDA receptor antagonists have been shown to prevent the manifestation of central sensitization as well as to decrease established hyperactivity in pain pathways. NMDA receptor antagonists play an important role in pain management.

Lack of Effect of Intrathecally Administered N-methyl-D-aspartate Receptor Antagonists in a Rat Model for Postoperative Pain 

1998 ◽  
Vol 88 (1) ◽  
pp. 143-156 ◽  
Author(s):  
Peter K. Zahn ◽  
Timothy J. Brennan
Keyword(s):  
Nmda Receptor ◽  
Postoperative Pain ◽  
Rat Model ◽  
Intrathecal Administration ◽  
Nmda Receptor Antagonist ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Mk 801 ◽  
Pain Behaviors ◽  
Plantar Incision

Background Evidence from experiments by others indicates an important role for excitatory amino acids activating spinal n-methyl-d-aspartate (NMDA) receptors in models of persistent pain. The purpose of this study was to examine the effect of intrathecal (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801), a noncompetitive NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (AP5), a competitive NMDA receptor antagonist, and N-G-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, on pain behaviors in a rat model of postoperative pain. Methods Rats with intrathecal catheters were anesthetized and underwent a plantar incision. Withdrawal threshold to punctate stimulation applied adjacent to the wound, response frequency to application of a nonpunctate stimulus applied directly to the wound, and nonevoked pain behaviors were measured before and after intrathecal administration of MK-801 or AP5. The effect of intrathecal L-NAME on mechanical hyperalgesia was also examined. Results Mechanical hyperalgesia increased and was persistent after plantar incision and was not decreased by intrathecal administration of 4, 14, or 40 nmol MK-801 or 10 nmol AP5. Only the greatest dose of AP5, 30 nmol, caused a small decrease in punctate and nonpunctate hyperalgesia. Intrathecal L-NAME had no effect. Neither intrathecal MK-801 nor intrathecal AP5 affected nonevoked pain behaviors. The greatest doses caused motor deficits. Conclusions Unlike intrathecal and systemic morphine, intrathecal NMDA receptor antagonists did not modify pain behaviors in this rat model of postoperative pain. These data suggest that NMDA receptors do not play an important role in the maintenance of postoperative pain behaviors and that NMDA receptor antagonists, administered spinally by themselves during the postoperative period, will not be useful for the treatment of postoperative pain in humans.

scholarly journals N-Methyl-D-Aspartate Antagonists in Levodopa Induced Dyskinesia: A Meta-Analysis

2012 ◽  
Vol 39 (4) ◽  
pp. 465-472 ◽  
Author(s):  
Behzad Elahi ◽  
Nicolás Phielipp ◽  
Robert Chen
Keyword(s):  
Clinical Trials ◽  
Nmda Receptor ◽  
Rating Scales ◽  
Rating Scale ◽  
Meta Analysis ◽  
Nmda Receptor Antagonists ◽  
Controlled Clinical Trials ◽  
Receptor Antagonists ◽  
Peak Dose ◽  
Standard Mean Difference

Background:Levodopa-induced dyskinesias (LID) are amongst the most disabling side-effects of levodopa therapy for Parkinson's disease (PD). It has been suggested that that N-Methyl-D-Aspartate (NMDA)-receptor antagonist may reduce peak-dose dyskinesia in PD patients and may lead to motor improvement. In this study, we compared the efficacy of NMDA receptor antagonists versus placebo in the treatment of LID in PD through a meta-analysis of controlled trials.Methods:Electronic search of Pubmed (1990 - 2010), Medline (1966-2010), EMBASE (1974-2010) and other databases for relevant studies were performed. Controlled clinical trials of the effects of NMDA antagonists on LID that fulfill the study protocol were selected. Pooled data from included studies was then used to perform random and fixed effect models meta-analysis.Results:The search resulted in 11 randomized, placebo controlled clinical trials that involved a total of 253 PD patients with peak-dose LID. The outcome measures were various dyskinesia rating scales and the Unified Parkinson Disease Rating Scale (UPDRS) subscales III and IV. The analysis showed significant reduction in Standard Mean Difference (SMD) for UPDRS IV (SMD -1.45; 95% CI -2.28 to -0.63) and UPDRS III (SMD -0.41; 95% CI -0.69 to -0.12) after treatment with amantadine. Other included drugs did not show significant change in the outcomes measured.Conclusion:This meta-analysis provides an update on the clinical trials and confirms the short-term benefits of amantadine therapy in the treatment of dyskinesia. The effects of other NMDA receptor antagonists need to be evaluated further in clinical trials.

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