The role of nitric oxide on the potentiating effect of magnesium on morphine analgesia

Abstract

Sir,Despite a lack of analgesic effectiveness by itself, magnesium potentiates the effect of analgesic drugs (1). This potentiating effect is suggested to be related to NMDA-receptor blockade (2) or inhibition of catecholamine release (3). But the mechanism is not clearly defined. Some studies demonstrated that nitric oxide (NO) modulates the transmission of pain (4). In addition, magnesium seems to alter NO synthesis (5). We thought that the analgesic effect of magnesium could be related to NO synthesis. Our study included three steps. We investigated firstly the analgesic effect of MgSO 4 used alone, secondly its potentiating effect on morphine sulphate (MS) analgesia, and lastly the effect of N G -Nitro L-Arginine Methyl Ester (L-NAME) on the analgesia offered by the combination of MS with MgSO 4 .After the approval of the Institutional Animal Care and Use Committee 77 mice were allocated into nine groups receiving the following drugs: Group 1 (n ¼ 8): no drug, group 2 (n ¼ 15): MS 1 mg kg À1 , group 3 (n ¼ 4): MgSO 4 1 g kg À1 , group 4 (n ¼ 13): MS 1 mg kg À1 þ MgSO 4 1 g kg À1 , group 5 (n¼ 7): MS 1 mg kg À1 þ MgSO 4 1 g kg À1 þ L-NAME 10 mg kg À1 , group 6 (n¼ 8): MS 0.1 mg kg À1 , group 7 (n¼ 5): MgSO 4 0.5 g kg À1 , group 8 (n¼ 10): MS 0.1 mg kg À1 þ MgSO 4 0.5 g kg À1 , and group 9 (n ¼ 7): MS 0.1 mg kg À1 þ MgSO 4 0.5 g kg À1 þ L-NAME 10 mg kg À1 . Before and 15, 30, 60, 120, 240 min after intraperitoneal drug injections, animals were placed on a hot plate, and the time to hind-paw licking or jumping was recorded as the hot-plate latency (HPL). The HPLs were compared within groups using Wilcoxon Signed Rank test and between groups using the Mann-Whitney U-test. P < 0.05 was considered statistically significant.Morphine sulphate used alone at two doses increased HPL. MgSO 4 used alone at two doses did not change HPL. Morphine sulphate 1 mg kg À1 combined with MgSO 4 1 g kg À1 increased HPL more than MS 1 mg kg À1 used alone. Morphine sulphate 0.1 mg kg À1 combined with MgSO 4 0.5 g kg À1 did not alter HPL when compared to MS 0.1 mg kg À1 used alone. When L-NAME was added to MS and MgSO 4 combinations, the HPL did not change.MgSO 4 did not offer analgesia when used alone and its potentiating effect on morphine analgesia was dose-related. These findings support the results of McCarthy's study (2). Our study was the first to investigate the role of NO on the analgesiapotentiating effect of MgSO 4 . As a NO synthase inhibitor, L-NAME added to the MS and MgSO 4 combination did not alter HPL, this potentiating effect seems not to be related to NO synthesis.

Evaluation of a single-dose of intravenous magnesium sulphate for prevention of postoperative pain after inguinal surgery

“…[6] The role of nitric oxide in potentiation of magnesium on morphine analgesia was discussed by Karaaslan and Arslan. [7]…”

The Effect of Intravenous Magnesium Sulfate on Acute Postoperative Bleeding in Elective Coronary Artery Bypass Surgery

“…Magnesium sulfate is a therapeutic solution with many uses (especially in cardiac surgery) including hemodynamic stability and analgesic effects, 7-12 although some considerations have been proposed regarding alterations in the coagulation system after administration of magnesium. [13][14][15][16][17] As previously mentioned, several studies, 1-3,6,12,14 including a recent evidence review, 14 explore the untoward effects of CAGB with CPB. Excessive bleeding, systematic inflammation, and several other disturbances are among the untoward effects of the bypass requiring more attention.…”

“…Magnesium has some anti-inflammatory effects through the production of nitric oxide, 12,13 which may overlap with the act of a few related proteins, both in the hemostatic and the inflammatory cascades. [9][10][11][12][13][14] These possible effects on the hemostatic and the inflammatory cascades may have a beneficial effect in reducing the amount of postoperative bleeding in patients undergoing CABG.…”

“…[9][10][11][12][13][14] These possible effects on the hemostatic and the inflammatory cascades may have a beneficial effect in reducing the amount of postoperative bleeding in patients undergoing CABG. [12][13][14] Limitations…”

“…2,3,6,7 A number of possible therapeutic effects (including anti-inflammatory effects) have been attributed to magnesium solutions, including magnesium sulfate. [7][8][9][10][11][12][13] It has been postulated that the anti-inflammatory effects of magnesium may have some relationship to the procoagulative and inflammatory cascade proteins, decreasing the activation of procoagulant and inflammatory proteins, which may finally decrease the amount of bleeding.…”