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Morphine Tolerance (morphine + tolerance)
Selected AbstractsMorphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. (National Medical Defense Center, Taipei, Taiwan) Br J Anaesth 2000;85:587,591.PAIN PRACTICE, Issue 2 2001Chih-Shung Wong N -Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance induced by intrathecal morphine infusion (10 ,g h,1) for 5 days. Co-administered MK801 with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-related rats than in control rats. There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord. Comment by Octavio Calvillo, M.D., Ph.D. Morphine tolerance may be due to receptor down-regulation or receptor uncoupling; activation of the NMDA-dependent pain-facilitatory system may also play a role. It has been proposed that NMDA receptor activation may play a role in morphine tolerance. NMDA receptor antagonists and nitric oxide synthase [NOS] inhibitors may prevent morphine tolerance. Tolerance was induced in rats by intrathecal injection of morphine [10 ug/h] for 5 days, co-administration of MK801 [NMDA antagonist] with morphine was used to prevent morphine tolerance. Lumbar spinal cord segments were removed and prepared for [H3]MK801 binding assays and NOS western blotting. The binding affinity of labeled MK801 was higher in spinal cords of morphine tolerant rats than in control rats. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine tolerant rats was twice that in the control group, thus, up-regulation was prevented by MK801. The results suggest that morphine tolerance affect NMDA receptor binding activity and increase neuronal protein expression in rat the spinal cord. [source] Stress-Induced Analgesia and Morphine Responses Are Changed in Catechol- O -methyltransferase-Deficient Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Oleg Kambur It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level. [source] G,, that interacts with adenylyl cyclase in opioid tolerance originates from a Gs proteinDEVELOPMENTAL NEUROBIOLOGY, Issue 12 2006Hoau-Yan Wang Abstract We previously demonstrated that chronic morphine induces a change in G protein coupling by the mu opioid receptor (MOR) from Gi/o to Gs, concurrent with the instatement of an interaction between G,, and adenylyl cyclase types II and IV. These two signaling changes confer excitatory effects on the cell in place of the typical inhibition by opioids and are associated with morphine tolerance and dependence. Both signaling changes and these behavioral manifestations of chronic morphine are attenuated by cotreatment with ultra-low-dose naloxone. In the present work, using striatum from chronic morphine-treated rats, we isotyped the G, within Gs and Go heterotrimers that coupled to MOR and compared these to the G, isotype of the G,, that interacted with adenylyl cyclase II or IV after chronic morphine treatment. Isotyping results show that chronic morphine causes a Gs heterotrimer associated with MOR to release its G,, to interact with adenylyl cyclase. These data suggest that the switch to Gs coupling by MOR in response to chronic morphine, which is attenuated by ultra-low-dose opioid antagonist cotreatment, leads to a two-pronged stimulation of adenylyl cyclase utilizing both G, and G,, subunits of the Gs protein novel to this receptor. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced morphine toleranceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2004Kazuaki Yokoyama Abstract Morphine is the drug of choice to treat intractable pain, although prolonged administration often causes undesirable side-effects including analgesic tolerance. It is speculated that voltage-dependent Ca2+ channels (VDCCs) play a key role in morphine analgesia and tolerance. To examine the subtype specificity of VDCCs in these processes, we analysed mice lacking N-type (Cav2.2) or R-type (Cav2.3) VDCCs. Systemic morphine administration or exposure to warm water swim-stress, known to induce endogenous opioid release, resulted in greater analgesia in Cav2.3,/, mice than in controls. Moreover, Cav2.3,/, mice showed resistance to morphine tolerance. In contrast, Cav2.2,/, mice showed similar levels of analgesia and tolerance to control mice. Intracerebroventricular (i.c.v.) but not intrathecal (i.t.) administration of morphine reproduced the result of systemic morphine in Cav2.3,/, mice. Furthermore, i.c.v. administration of an R-type channel blocker potentiated morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca2+ current could lead to high-efficiency opioid therapy without tolerance. [source] Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. (National Medical Defense Center, Taipei, Taiwan) Br J Anaesth 2000;85:587,591.PAIN PRACTICE, Issue 2 2001Chih-Shung Wong N -Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance induced by intrathecal morphine infusion (10 ,g h,1) for 5 days. Co-administered MK801 with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-related rats than in control rats. There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord. Comment by Octavio Calvillo, M.D., Ph.D. Morphine tolerance may be due to receptor down-regulation or receptor uncoupling; activation of the NMDA-dependent pain-facilitatory system may also play a role. It has been proposed that NMDA receptor activation may play a role in morphine tolerance. NMDA receptor antagonists and nitric oxide synthase [NOS] inhibitors may prevent morphine tolerance. Tolerance was induced in rats by intrathecal injection of morphine [10 ug/h] for 5 days, co-administration of MK801 [NMDA antagonist] with morphine was used to prevent morphine tolerance. Lumbar spinal cord segments were removed and prepared for [H3]MK801 binding assays and NOS western blotting. The binding affinity of labeled MK801 was higher in spinal cords of morphine tolerant rats than in control rats. Western blot analysis showed that constitutive expression of neuronal NOS protein in the morphine tolerant rats was twice that in the control group, thus, up-regulation was prevented by MK801. The results suggest that morphine tolerance affect NMDA receptor binding activity and increase neuronal protein expression in rat the spinal cord. [source] Stress-Induced Analgesia and Morphine Responses Are Changed in Catechol- O -methyltransferase-Deficient Male MiceBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2008Oleg Kambur It is not clear how the effects of COMT are mediated and only few relevant animal studies have been performed. Here, we used old male Comt gene knock-out mice as an animal model to study the effects of COMT deficiency on nociception that was assessed by the hot plate and tail flick tests. Stress-induced analgesia was achieved by forced swim. Morphine antinociception was measured after 10 mg/kg of morphine subcutaneously. Morphine tolerance was produced with subcutaneous morphine pellets and withdrawal provoked with subcutaneous naloxone. In the hot plate test, morphine-induced antinociception was significantly greater in the COMT knock-out mice, compared to the wild-type mice. This may be due to increased availability of opioid receptors as suggested by previous human studies. In the tail flick test, opioid-mediated stress-induced analgesia was absent and morphine-induced analgesia was decreased in COMT knock-out mice. In the hot plate test, stress-induced analgesia developed to all mice regardless of the COMT genotype. There were no differences between the genotypes in the baseline nociceptive thresholds, morphine tolerance and withdrawal. Our findings show, for the first time, the importance of COMT activity in stress- and morphine-induced analgesia in mice. COMT activity seems to take part in the modulation of nociception not only in the brain, as suggested earlier, but also at the spinal/peripheral level. [source] | |||||||||||||