Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs). Morphine is an agonist of mu-opioid receptors and inhibits N-type VSCC channels via a G-protein coupling mechanism. Both agents are antinociceptive when they are administered intrathecally (spinally). The present study investigated the acute and chronic (7-day) interactions of intrathecally administered ziconotide and morphine on nociception in several animal models of pain. In the acute study, intrathecal bolus injections of morphine and ziconotide alone produced dose-dependent inhibition of formalin-induced tonic flinch responses and withdrawal responses to paw pressure. The combination of ziconotide and morphine produced an additive inhibition of formalin-induced tonic flinch responses and a significant leftward shift of the morphine dose-response curve in the paw pressure test. After chronic (7-day) intrathecal infusion, ziconotide enhanced morphine analgesia in the formalin test. In contrast, chronic intrathecal morphine infusion produced tolerance to analgesia, but did not affect ziconotide antinociception. Antinociception produced by ziconotide alone was the same as that observed when the compound was co-administered with morphine to morphine-tolerant rats. In the hot-plate and tail immersion tests, chronic intrathecal infusion of morphine lead to rapid tolerance whereas ziconotide produced sustained analgesia with no loss of potency throughout the infusion period. Although ziconotide in combination with morphine produced an apparent synergistic analgesic effects during the initial phase of continuous infusion, it did not prevent morphine tolerance to analgesia. These results demonstrate that (1) acute intrathecal administrations of ziconotide and morphine produce additive or synergistic analgesic effects; (2) chronic intrathecal morphine infusion results in tolerance to analgesia but does not produce cross-tolerance to ziconotide; (3) chronic intrathecal ziconotide administration produces neither tolerance nor cross-tolerance to morphine analgesia; (4) intrathecal ziconotide does not prevent or reverse morphine tolerance.

Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally. It is currently under clinical investigation for the treatment of malignant and non-malignant pain syndromes. The present study was undertaken to compare and contrast antinociceptive properties of ziconotide, morphine and clonidine in a rat model of post-operative pain. Post-operative pain was produced by making a longitudinal incision through the skin, fascia, and muscle of the plantar aspect of the left hindpaw. This procedure produced immediate (0.5 h after surgery) and long-lasting (4-7 days post-surgery) heat hyperalgesia and mechanical allodynia in the injured hindpaw. Pain thresholds in the contralateral hindpaw were unaffected. Administered one day after incisional surgery, intrathecal ziconotide blocked established heat hyperalgesia in the injured hindpaw in a dose-dependent manner yielding an ED(50)4 h) but reversible (<24 h) blockade of established mechanical allodynia. Administered one day after surgery, intrathecal bolus injection of morphine dose-dependently blocked heat hyperalgesia in the injured hindpaw with an ED(50) of 1.6 microg (2.1 nmol) and heat nociceptive responses in the normal hindpaw with an ED(50) of 2.7 microg (3.6 nmol). The effects were immediate and short-lasting (

Objective.To investigate the effects of morphine postconditioning on Myocardial ischemia reperfusion injury in rats in vivo. Methods. To randomly divide 40 male SD rats equally into 4 groups, including Sham group in which the chest was opened without ligating the left coronary artery, ischemia-reperfusion group(Group I/R ), ischemic preconditioning group(Group IPC ) and morphine postconditioning group(GroupMOR) in which 0. 3 mg/kg morphine was given intravenously 5 min before reperfusion. The left anterior descending coronary arterys(LAD) of rats in five groups are ligated for 30 minutes and are re-perfused for 90 minutes. Cardiac Apoptosis was determined quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） methods． To calculate the concentration of the serum malondialdehyde(MDA) with Thiobarbituric acid (TBA) reaction method and the activity of the superoxide dismutase (SOD) with xanthine oxidase reaction method. Result. Comparing with Group S, the quantity of the cardiac apoptosis in Group I/R, IPC and MOR rised in different levels. Comparing with Group 1/R, the quantity of the cardiac apoptosis in Group IPC and MOR reduced obviously. Comparing with Group 1/R, the concentration of the serum malondialdehyde (MDA) in the other four groups all reduced and the activity of the superoxide dismutase increased. Conclusion. Morphine postconditioning can significantly reduce myocardial apoptosis induced by ischemia-reperfusion injury，reduce myocardial infarct size, decrease the concentration of MDA, and increase the activity of SOD. Therefore, morphine postconditioning has protective effects on myocardial ischemia-reperfusion injury in rats in vivo. Morphine is a potent kind of opioid analgesics, which is widely used in clinical anesthesia. However, further studies are needed on effects of morphine postconditioning on myocardial ischemia reperfusion injury. In order to provide the foundations for clinical application, the authors investigate the effects of morphine postconditioning on myocardial ischemia reperfusion injury through comparison and analysis of the cardiac apoptosis, the concentration of the serum malondialdehyde (MDA) and the activity of the superoxide dismutase (SOD) in Group S, I/R, IPC and MOR.

Objective.To investigates the effects of sufentanil post conditioning on Myocardial ischemia reperfusion injury in rats in vivo.Methods.To randomly divide 40 male SD rats equally into 4 groups, including Sham group, ischemia-reperfusion group (Group I/R ), ischemic post conditioning group (Group IPO) and sufentanil post conditioning group (Group SUF). The left anterior descending coronary arterys (LAD) of rats in 4 groups are ligated for 30 minutes and are re-perfused for 120 mins. To measure the myocardial infarction size (IS/AAR%) with double-staining with Even's blue and triphenyltetrazolium chloride, to calculate the concentration of cTnI, and to observe the HE staining and the expression of Bcl-2 and Bax.Result. Comparing with Group 1/R, the myocardial infarction size (IS/AAR%), and the concentration of cTnI in Group IPO and SUF all reduced significantly. Comparing with Group 1/R, cell morphological observation shows less change in pathology. And the expression of Bcl-2 increases and expression of Bax decreases in Group IPO and SUF than that in Group 1/R.Conclusion. Sufentanil post conditioning has protective effects on myocardial ischemia-reperfusion injury in rats in vivo.

Objective.To investigate the effects of sufentanil preconditioning on Myocardial ischemia reperfusion injury in rats in vivo.Methods. To randomly divide 50 male SD rats equally into 5 groups, including ischemia-reperfusion group( Group I/R ), ischemic preconditioning group(Group IPC), high-dose sufentanil preconditioning group(Group HS, 6.0µg/kg), medium-dose sufentanil preconditioning group(Group MS,2.0µg/kg) and low-dose sufentanil preconditioning group(Group LS, 0.60µg/kg).The left anterior descending coronary arterys(LAD) of rats in five groups are ligated for 30 minutes and are re-perfused for 90 minutes. To measure the myocardial infarction size (IS/AAR%) with double-staining with Even's blue and triphenyltetrazolium chloride, and to calculate the concentration of LK, LK-MB and LDH. Result. Comparing with Group 1/R , the myocardial infarction size(IS/AAR%) in Group IPC, HS, MS and LS all reduced at different levels. Among the Group HS, MS and LS, the infarction size in Group HS reduced most significantly. Comparing with Group 1/R, the concentration of the serum myocardial enzymes in the other four groups all reduced at different levels. Conclusion. Sufentanil preconditioning can reduce myocardial infarct size, decrease the concentration of the serum myocardial enzymes. Therefore, sufentanil preconditioning has protective effects on myocardial ischemia-reperfusion injury in rats in vivo, and the effects are dose-dependent. Suffentanil is a potent kind of opioid analgesics, which is widely used in clinical anesthesia. However, further studies are needed on effects of sufentanil preconditioning on myocardial ischemia reperfusion injury. In order to protect the Myocardial ischemia patients and provide the foundations for application of sufentanil in peri-operative period, the authors investigate the effects of sufentanil preconditioning on myocardial ischemia reperfusion injury through comparison and analysis of the myocardial infarction size(IS), the concentration of the serum myocardial enzymes in the ischemia-reperfusion group(Group IPC), the ischemic preconditioning group(Group IPC) and different-dose sufentanil preconditioning group(Group HS, MS LS).