European journal of pharmacology
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Diabetes mellitus has been known to mitigate ischemic or pharmacologic preconditioning in ischemia-reperfusion injuries. Remifentanil is a widely used opioid in cardiac anesthesia that possesses a cardioprotective effect against ischemia-reperfusion. We evaluated whether diabetes affected remifentanil preconditioning induced cardioprotection in ischemia-reperfusion rat hearts in view of anti-apoptotic pathways of survival and Ca(2+) homeostasis. ⋯ In diabetic rat hearts, however, remifentanil preconditioning failed to recover the phosphorylation state of ERK1/2 and to repress apoptotic signaling. In addition, diabetes minimized remifentanil induced modulation of abnormal changes in sarcoplasmic reticulum genes and proteins in ischemia-reperfusion rat hearts. In conclusion, diabetes mitigated remifentanil induced cardioprotection against ischemia-reperfusion, which might be associated with reduced recovery of the activities of proteins involved in anti-apoptotic pathways including ERK1/2 and the abnormal expression of sarcoplasmic reticulum genes as a result of ischemia-reperfusion in rat hearts.
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Antiepileptic and antidepressant drugs are the primary treatments for pain relief in diabetic neuropathy. Combination therapy is a valid approach in pain treatment, where a reduction of doses could reduce side effects and still achieve optimal analgesia. We examined the effects of two-drug combinations of gabapentin, oxcarbazepine, and amitriptyline on nociception in diabetic mice and aimed to determine the type of interaction between components. ⋯ Oxcarbazepine (10-60mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) and gabapentin (10-30mg/kg; p.o.)+amitriptyline (5mg/kg; p.o.) combinations significantly and dose-dependently reduced nociception in diabetic mice. Analysis of the log dose-response curves for oxcarbazepine or gabapentin in a presence of amitriptyline and oxcarbazepine or gabapentin applied alone, revealed a synergism in oxcarbazepine-amitriptyline and additivity in gabapentin-amitriptyline combination. These findings provide new information about the combination therapy of painful diabetic neuropathy and should be explored further in patients with diabetic neuropathy.
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Itching is known as a commonly side effect of opioid administration. However, the relationship of opioid receptors to itching is unclear. In this study, we examined the effect of intradermal injection of morphine and fentanyl on the itching sensation. ⋯ Additionally, scratching behavior induced by morphine and fentanyl were not suppressed by glucocorticoids (predonisolone and dexamethasone). In conclusion, opioid-induced itching may involve in peripheral opioid receptors. Moreover, histamine and arachidonic acid metabolites played no main role in opioid-induced scratching behavior.
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The aim of this study was to examine the involvement of 5-HT and 5-HT(2A) receptors in neuropathic pain and their possible cellular mechanism. To evaluate a potential therapy the 5-HT(2A) receptor antagonist ketanserin was administered topically or subcutaneously in rats with L5 nerve ligation. Unilateral spinal nerve ligation induced hypersensitivity to thermal and mechanical stimuli in the ipsilateral hindpaw and an increase in calcitonin gene-related peptide (CGRP) immunoreactivity (CGRP-IR) in small and medium diameter neurons in dorsal root ganglia (DRG) at L4 and L6, but not at L5. ⋯ Moreover, ketanserin (0.3mg/kg) reversed the increase in CGRP-IR expression in L4 and L6 DRG neurons. These results support the hypothesis that adaptive change in CGRP expression that occurred in the DRG adjacent to the DRG containing injured neurons underlies the nerve ligation-induced hypersensitivity. This study suggests that 5-HT and 5-HT(2A) receptors contribute to the maintenance of neuropathic pain by up-regulating the expression of CGRP-IR, and that topical and systemic administrations of ketanserin are promising therapies for relieving neuropathic pain without tolerance.
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Brain neuronal histamine, through its receptors, is involved in central pain perception. In the present study, the effect of microinjection of histamine, mepyramine (a histamine H(1) receptor antagonist) and ranitidine (a histamine H(2) receptor antagonist) into the dorsal hippocampus was investigated on a model of orofacial pain in rats. Orofacial pain was induced by subcutaneous injection of formalin (1%, 50 microl) in the upper lip in rats, and the time spent of face rubbing was measured in 3-min blocks for 45 min. ⋯ Pretreatments with mepyramine and ranitidine at a same dose of 4 microg prevented histamine (1 microg)-induced antinociception. These results indicate that the activation of brain neuronal histamine at the levels of the hippocampus may produce antinociception. Hippocampal histamine-induced antinociception may be mediated thorough its H(1) and H(2) receptors.