Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Anesthesiology
Published in: BMC Anesthesiology 1/2017

Open Access 01-12-2017 | Research article

Magnesium sulphate attenuate remifentanil-induced postoperative hyperalgesia via regulating tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord

Authors: Jiehao Sun, Hai Lin, Guodong He, Wendong Lin, Jianping Yang

Published in: BMC Anesthesiology | Issue 1/2017

Login to get access

Abstract

Background

Remifentanil induced hyperalgesia (RIH) is characterized by stimulation evoked pain including allodynia and thermal hyperalgesia after remifentanil infusion. N-methyl-D-aspartate (NMDA) receptor was reported to be involved in the progress of RIH. We hypothesized that intrathecal MgSO4 could relieve hyperalgesia after remifentanil infusion via regulating phosphorylation of NMDA receptor NR2B subunit activity in this study.

Methods

Thirty two rats were randomly allocated into control group, model of RIH group, RIH plus 100ug MgSO4 group, RIH plus 300ug MgSO4 group. Mechanical and thermal hyperalgesia were tested at -24th h, 2nd h, 6th h, 24th h, 48th h after remifentanil infusion. Following sacrifice of rats after the last behavioral test, we performed the western blot to detect the expression of spinal phosphorylated NMDA receptor NR2B subunit (pNR2B) in the L4-L5 segments.

Results

Intrathecal MgSO4 (100, 300 μg) dose-dependently reduced thermal and mechanical hyperalgesia from 2 h to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of pNR2B. Nevertheless, the increased amount of pNR2B by RIH was dose-dependently suppressed by intrathecal infusion of MgSO4 in rats.

Conclusions

Remifentanil induced hyperalgesia/allodynia could be ameliorated by Mg-mediated blockade targeting the NR2B subunit in NMDA receptors.
Appendix
Available only for authorised users
Literature
1.
Shin SW, Cho AR, Lee HJ, Kim HJ, Byeon G, Yoon JW, Kim KH, Kwon JY. Maintenance anaesthetics during remifentanil-based anaesthesia might affect postoperative pain control after breast Cancer. Br J Anaesth. 2010;105:661–7.CrossRefPubMed
2.
Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, Fletcher D, Chauvin M. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000;93:409–17.CrossRefPubMed
3.
Zhao M, Joo DT. Enhancement of spinal N-methyl-D-aspartate receptor function by remifentanil action at delta-opioid receptors as a mechanism for acute opioid-induced hyperalgesia or tolerance. Anesthesiology. 2008;109:308–17.CrossRefPubMed
4.
Dunah AW, Wang Y, Yasuda RP, Kameyama K, Huganir RL, Wolfe BB, Standaert DG. Alterations in subunit expression, composition, and phosphorylation of striatal N-methyl-D-aspartate glutamate receptors in a rat 6-hydroxydopamine model of Parkinson’s disease. Mol Pharmacol. 2000;57:342–52.PubMed
5.
Jiang M, Zhang W, Ma Z, Gu X. Antinociception and prevention of hyperalgesia by intrathecal administration of Ro 25–6981, a highly selective antagonist of the 2B subunit of N-methyl-D-aspartate receptor. Pharmacol Biochem Behav. 2013;112:56–63.CrossRefPubMed
6.
Angst MS, Koppert W, Pahl I, Clark DJ, Schmelz M. Short-term infusion of the mu-opioid agonist remifentanil in humans causes hyperalgesia during withdrawal. Pain. 2003;106:49–57.CrossRefPubMed
7.
Van Elstraete AC, Sitbon P, Mazoit J-X, Conti M, Benhamou D. Protective effect of prior administration of magnesium on delayed hyperalgesia induced by fentanyl in rats. Can J Anesth. 2006;53:1180–5.CrossRefPubMed
8.
Tufan M, Yasemin G, Dilek O, Ismail G. Magnesium modifies fentanyl-induced local antinociception and hyperalgesia. Naunyn Schmiedebergs Arch Pharmacol. 2009;380:415–20.CrossRef
9.
Sun J, Lin H, Feng X, Dong J, Ansong E, Xu X. A comparison of intrathecal magnesium and ketamine in attenuating remifentanil-induced hyperalgesia in rats. BMC Anesthesiol. 2016;16:74.CrossRefPubMedPubMedCentral
10.
Yoshito T, Eiru S, Toshihiko K, Isao S. Antihyperalgesic effects of intrathecally administered magnesium sulfate in rats. Pain. 2000;84:175–9.CrossRef
11.
Rondon LJ, Privat AM, Daulhac L, Davin N, Mazur A, Fialip J, Eschalier A, Courteix C. Magnesium attenuates chronic hypersensitivity and spinal cord NMDA receptor phosphorylation in a rat model of diabetic neuropathic pain. J Physiol. 2010;588:4205–15.CrossRefPubMedPubMedCentral
12.
Waxman AR, Arout C, Caldwell M, Dahan A, Kest B. Acute and chronic fentanyl administration causes hyperalgesia independently of opioid receptor activity in mice. Neurosci Lett. 2009;46:68–72.CrossRef
13.
Juni A, Klein G, Pintar JE, Kest B. Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience. 2007;147:439–44.CrossRefPubMed
14.
Guntz E, Dumont H, Roussel C, Gall D, Dufrasne F, Cuvelier L, Blum D, Schiffmann SN, Sosnowski M. Effects of remifentanil on N-methyl-D-aspartate receptor: an electrophysiologic study in rat spinal cord. Anesthesiology. 2005;102:1235–41.CrossRefPubMed
15.
Parisa H, Mohsen P, Mansoor K, Kazem J, Marzieh M, Nepton S. Oral magnesium administration prevents thermal hyperalgesia induced by diabetes in rats. Diabetes Res Clin Pract. 2006;73:17–22.CrossRef
16.
Ossipov MH, Lai J, King T, Vanderah TW, Malan TP, Hruby VJ, Porreca F. Antinociceptive and nociceptive actions of opioids. J Neurobiol. 2004;61:126–48.CrossRefPubMed
17.
Nagy GG, Watanabe M, Fukaya M, Todd AJ. Synaptic distribution of the NR1, NR2A and NR2B subunits of the N-methyl-d-aspartate receptor in the rat lumbar spinal cord revealed with an antigen-unmasking technique. Eur J Neurosci. 2004;20:3301–12.CrossRefPubMed
18.
Wilson JA, Garry EM, Anderson HA, Rosie R, Colvin LA, Mitchell R, Fleetwood-Walker SM. NMDA receptor antagonist treatment at the time of nerve injury prevents injury-induced changes in spinal NR1 and NR2B subunit expression and increases the sensitivity of residual pain behaviours to subsequently administered NMDA receptor antagonists. Pain. 2005;117:421–32.CrossRefPubMed
19.
Nakazawa T, Komai S, Tezuka T, Hisatsune C, Umemori H, Semba K, Mishina M, Manabe T, Yamamoto T. Characterization of Fynmediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. J Biol Chem. 2001;276:693–9.CrossRefPubMed
20.
Abe T, Matsumura S, Katano T, Mabuchi T, Takagi K, Xu L, Yamamoto A, Hattori K, Yagi T, Watanabe M, Nakazawa T, Mishina M, Nakai Y, Ito S. Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain. Eur J Neurosci. 2005;22:1445–54.CrossRefPubMed
21.
Guo W, Zou S, Guan Y, Ikeda T, Tal M, Dubner R, Ren K. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J Neurosci. 2002;22:6208–17.PubMed
22.
Drdla R, Gassner M, Gingl E, Sandkühler J. Induction of synaptic long-term potentiation after opioid withdrawal. Science. 2009;325:207–10.CrossRefPubMed
23.
Gu XP, Wu XL, Liu Y, Cui SQ, Ma ZL. Tyrosine phosphorylation of the N-Methyl-D-Aspartate receptor 2B subunit in spinal cord contributes to remifentanil-induced postoperative hyperalgesia: the preventive effect of ketamine. Mol Pain. 2009;5:76–84.CrossRefPubMedPubMedCentral
24.
Célérier E, González JR, Maldonado R, Cabalvro D, Puig MM. Opioid-induced hyperalgesia in a murine model of postoperative pain: role of nitric oxide generated from the inducible nitric oxide synthase. Anesthesiology. 2006;104:546–55.CrossRefPubMed
25.
Wang CY, Li YZ, Wang HY, Xie KL, Shu RC, Zhang LL, Hu N, Yu YH, Wang GL. Inhibition of DOR prevents remifentanil induced postoperative hyperalgesia through regulating the trafficking and function of spinal NMDA receptors in vivo and in vitro. Brain Res Bull. 2015;110:30–9.CrossRefPubMed
Metadata
Title
Magnesium sulphate attenuate remifentanil-induced postoperative hyperalgesia via regulating tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord
Authors
Jiehao Sun
Hai Lin
Guodong He
Wendong Lin
Jianping Yang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2017
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-017-0325-3

Other articles of this Issue 1/2017

BMC Anesthesiology 1/2017 Go to the issue

Research article

Tracheal extubation in deeply anesthetized pediatric patients after tonsillectomy: a comparison of high-concentration sevoflurane alone and low-concentration sevoflurane in combination with dexmedetomidine pre-medication

Research article

Adequate interval for the monitoring of vital signs during endotracheal intubation

Research article

Minimal shedding of the glycocalyx layer during abdominal hysterectomy

Research article

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS

Case report

Management of intra-operative acute pulmonary embolism during general anesthesia: a case report

Research article

Does local infiltration analgesia reduce peri-operative inflammation following total hip arthroplasty? A randomized, double-blind study