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Modulation of cholestasis-induced antinociception in rats by two NMDA receptor antagonists: MK-801 and magnesium sulfate.
Eur J Pharmacol. 2007 Jan 12; 554(2-3):123-7.EJ

Abstract

Acute cholestasis is associated with increased activity of the endogenous opioid system that results to changes including analgesia. N-methyl-d-aspartate (NMDA) receptors are involved in the nociceptive pathway and play a major role in the development of morphine induced analgesia. The magnesium acts as a non-competitive NMDA receptor antagonist by blocking the NMDA receptor channel. Considering the reported antinociceptive effect of magnesium sulfate as a NMDA receptor antagonist and the existence of close functional links between NMDA receptor antagonists and magnesium with the opioid system, we studied the effect of acute and chronic administration of MK-801 as a NMDA antagonist and magnesium sulfate on modulation of nociception in an experimental model of elevated endogenous opioid tone, acute cholestasis, using the tail-flick paradigm. Cholestasis was induced by ligation of the main bile duct using two ligatures and then transsection of the duct at the midpoint between them. A significant increase (P<0.001) in nociception threshold was observed in bile duct ligated rats compared to unoperated and sham-operated animals. In acute treatment, MK-801 (0.1 mg/kg, b.i.d), but not magnesium (150 mg/kg magnesium sulfate, i.e. 30 mg/kg of Mg(+2), i.p., b.i.d.) increased antinociception in cholestatic rats compared to saline treated cholestatics (P<0.05). In chronic treatment, administration of MK-801 or magnesium sulfate for 7 consecutive days, increased tail-flick latency (P<0.05, P<0.01) in cholestatic animals compared to saline treated cholestatics. These data showed that NMDA receptor pathway is involved in modulation of cholestasis-induced antinociception in rats and that repeated dosages of magnesium sulfate similar to MK-801 is able to modulate nociception in cholestasis.

Authors+Show Affiliations

Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17107671

Citation

Hasanein, Parisa, et al. "Modulation of Cholestasis-induced Antinociception in Rats By Two NMDA Receptor Antagonists: MK-801 and Magnesium Sulfate." European Journal of Pharmacology, vol. 554, no. 2-3, 2007, pp. 123-7.
Hasanein P, Parviz M, Keshavarz M, et al. Modulation of cholestasis-induced antinociception in rats by two NMDA receptor antagonists: MK-801 and magnesium sulfate. Eur J Pharmacol. 2007;554(2-3):123-7.
Hasanein, P., Parviz, M., Keshavarz, M., Javanmardi, K., Allahtavakoli, M., & Ghaseminejad, M. (2007). Modulation of cholestasis-induced antinociception in rats by two NMDA receptor antagonists: MK-801 and magnesium sulfate. European Journal of Pharmacology, 554(2-3), 123-7.
Hasanein P, et al. Modulation of Cholestasis-induced Antinociception in Rats By Two NMDA Receptor Antagonists: MK-801 and Magnesium Sulfate. Eur J Pharmacol. 2007 Jan 12;554(2-3):123-7. PubMed PMID: 17107671.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of cholestasis-induced antinociception in rats by two NMDA receptor antagonists: MK-801 and magnesium sulfate. AU - Hasanein,Parisa, AU - Parviz,Mohsen, AU - Keshavarz,Mansoor, AU - Javanmardi,Kazem, AU - Allahtavakoli,Mohammad, AU - Ghaseminejad,Majid, Y1 - 2006/10/19/ PY - 2006/04/23/received PY - 2006/09/26/revised PY - 2006/10/02/accepted PY - 2006/11/17/pubmed PY - 2007/3/7/medline PY - 2006/11/17/entrez SP - 123 EP - 7 JF - European journal of pharmacology JO - Eur. J. Pharmacol. VL - 554 IS - 2-3 N2 - Acute cholestasis is associated with increased activity of the endogenous opioid system that results to changes including analgesia. N-methyl-d-aspartate (NMDA) receptors are involved in the nociceptive pathway and play a major role in the development of morphine induced analgesia. The magnesium acts as a non-competitive NMDA receptor antagonist by blocking the NMDA receptor channel. Considering the reported antinociceptive effect of magnesium sulfate as a NMDA receptor antagonist and the existence of close functional links between NMDA receptor antagonists and magnesium with the opioid system, we studied the effect of acute and chronic administration of MK-801 as a NMDA antagonist and magnesium sulfate on modulation of nociception in an experimental model of elevated endogenous opioid tone, acute cholestasis, using the tail-flick paradigm. Cholestasis was induced by ligation of the main bile duct using two ligatures and then transsection of the duct at the midpoint between them. A significant increase (P<0.001) in nociception threshold was observed in bile duct ligated rats compared to unoperated and sham-operated animals. In acute treatment, MK-801 (0.1 mg/kg, b.i.d), but not magnesium (150 mg/kg magnesium sulfate, i.e. 30 mg/kg of Mg(+2), i.p., b.i.d.) increased antinociception in cholestatic rats compared to saline treated cholestatics (P<0.05). In chronic treatment, administration of MK-801 or magnesium sulfate for 7 consecutive days, increased tail-flick latency (P<0.05, P<0.01) in cholestatic animals compared to saline treated cholestatics. These data showed that NMDA receptor pathway is involved in modulation of cholestasis-induced antinociception in rats and that repeated dosages of magnesium sulfate similar to MK-801 is able to modulate nociception in cholestasis. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17107671/Modulation_of_cholestasis_induced_antinociception_in_rats_by_two_NMDA_receptor_antagonists:_MK_801_and_magnesium_sulfate_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(06)01119-8 DB - PRIME DP - Unbound Medicine ER -