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      The effects of magnesium sulfate infiltration on perioperative opioid consumption and opioid-induced hyperalgesia in patients undergoing robot-assisted laparoscopic prostatectomy with remifentanil-based anesthesia

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          Abstract

          Background

          Opioids not only exert an antinociceptive effect, but also modulate central N-methyl-D-aspartate (NMDA) receptors, resulting in hyperalgesia and acute opioid tolerance. This study was aimed to investigate the effect of the NMDA receptor antagonist, magnesium in preventing remifentanil-induced hyperalgesia.

          Methods

          For this study, 75 patients scheduled for robot-assisted laparoscopic prostatectomy were randomly allocated into three groups of patients whose incision sites were infiltrated: Group M, with 25% magnesium sulfate 80 mg/kg; Group S, with the same volume of saline under remifentanil-based anesthesia, and Group D, with the same volume of saline under desflurane based anesthesia. All three groups were infiltrated into incision sites after pneumoperitoneum. Intraoperative evaluation included mean remifentanil dose, and postoperative evaluation included pain severity at time intervals of 30 min, 6, 12, 24 and 36 hours, time to first postoperative analgesic requirement, and analgesic dosage required during 24 hours.

          Results

          Mean remifentanil doses during the intraoperative periods in group M were significantly lower than those in group S (P < 0.001). The time to first postoperative analgesic requirement in postoperative period in groups M and D was significantly longer than that in group S (P < 0.001). Visual analog scale scores for pain in groups M and D were significantly lower than those in group S for 12 hours after operation.

          Conclusions

          A relatively high dose and continuous infusion of remifentanil were associated with opioid induced hyperalgesia. Wound infiltration with magnesium sulfate decreased opioid consumption and reduces opioid induced hyperalgesia.

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          Most cited references25

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          Magnesium gates glutamate-activated channels in mouse central neurones.

          The responses of vertebrate neurones to glutamate involve at least three receptor types. One of these, the NMDA receptor (so called because of its specific activation by N-methyl-D-aspartate), induces responses presenting a peculiar voltage sensitivity. Above resting potential, the current induced by a given dose of glutamate (or NMDA) increases when the cell is depolarized. This is contrary to what is observed at classical excitatory synapses, and recalls the properties of 'regenerative' systems like the Na+ conductance of the action potential. Indeed, recent studies of L-glutamate, L-aspartate and NMDA-induced currents have indicated that the current-voltage (I-V) relationship can show a region of 'negative conductance' and that the application of these agonists can lead to a regenerative depolarization. Furthermore, the NMDA response is greatly potentiated by reducing the extracellular Mg2+ concentration [( Mg2+]o) below the physiological level (approximately 1 mM). By analysing the responses of mouse central neurones to glutamate using the patch-clamp technique, we have now found a link between voltage sensitivity and Mg2+ sensitivity. In Mg2+-free solutions, L-glutamate, L-aspartate and NMDA open cation channels, the properties of which are voltage independent. In the presence of Mg2+, the single-channel currents measured at resting potential are chopped in bursts and the probability of opening of the channels is reduced. Both effects increase steeply with hyperpolarization, thereby accounting for the negative slope of the I-V relationship of the glutamate response. Thus, the voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependence of the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent 'gate'.
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            The role of N-methyl-D-aspartate (NMDA) receptors in pain: a review.

            There is accumulating evidence to implicate the importance of N-methyl-D-aspartate (NMDA) receptors to the induction and maintenance of central sensitization during pain states. However, NMDA receptors may also mediate peripheral sensitization and visceral pain. NMDA receptors are composed of NR1, NR2 (A, B, C, and D), and NR3 (A and B) subunits, which determine the functional properties of native NMDA receptors. Among NMDA receptor subtypes, the NR2B subunit-containing receptors appear particularly important for nociception, thus leading to the possibility that NR2B-selective antagonists may be useful in the treatment of chronic pain.
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              Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine.

              Remifentanil-induced secondary hyperalgesia has been documented experimentally in both animals and healthy human volunteers, but never clinically. This study tested the hypotheses that increased pain sensitivity assessed by periincisional allodynia and hyperalgesia can occur after relatively large-dose intraoperative remifentanil and that small-dose ketamine prevents this hyperalgesia. Seventy-five patients undergoing major abdominal surgery were randomly assigned to receive (1) intraoperative remifentanil at 0.05 microg x kg(-1) x min(-1) (small-dose remifentanil); (2) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) (large-dose remifentanil); or (3) intraoperative remifentanil at 0.40 microg x kg(-1) x min(-1) and 0.5 mg/kg ketamine just after the induction, followed by an intraoperative infusion of 5 microg x kg(-1) x min(-1) until skin closure and then 2 microg x kg(-1) x min(-1) for 48 h (large-dose remifentanil-ketamine). Pain scores and morphine consumption were recorded for 48 postoperative hours. Quantitative sensory tests, peak expiratory flow measures, and cognitive tests were performed at 24 and 48 h. Hyperalgesia to von Frey hair stimulation adjacent to the surgical wound and morphine requirements were larger (P < 0.05) and allodynia to von Frey hair stimulation was greater (P < 0.01) in the large-dose remifentanil group compared with the other two groups, which were comparable. There were no significant differences in pain, pressure pain detection threshold with an algometer, peak flow, cognitive tests, or side effects. A relatively large dose of intraoperative remifentanil triggers postoperative secondary hyperalgesia. Remifentanil-induced hyperalgesia was prevented by small-dose ketamine, implicating an N-methyl-d-aspartate pain-facilitator process.
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                Author and article information

                Journal
                Korean J Anesthesiol
                KJAE
                Korean Journal of Anesthesiology
                The Korean Society of Anesthesiologists
                2005-6419
                2005-7563
                September 2011
                23 September 2011
                : 61
                : 3
                : 244-250
                Affiliations
                [1 ]Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, Iksan, Korea.
                [2 ]Department of Obstetrics and Gynecology, Wonkwang University School of Medicine, Iksan, Korea.
                Author notes
                Corresponding author: Cheol Lee, M.D., Department of Anesthesiology and Pain Medicine, Wonkwang University School of Medicine, 344-2, Sinyong-dong, Iksan 570-749, Korea. Tel: 82-63-850-1560, Fax: 82-63-857-5472, ironyii@ 123456wonkwang.ac.kr
                Article
                10.4097/kjae.2011.61.3.244
                3198187
                22025948
                e79b7ee5-cf1e-42d2-9fce-c31ac0975372
                Copyright © the Korean Society of Anesthesiologists, 2011

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 December 2010
                : 14 March 2011
                : 14 March 2011
                Categories
                Clinical Research Article

                Anesthesiology & Pain management
                magnesium sulfate,nmda receptor,remifentanil,opioid induced hyperalgesia

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