European journal of pharmacology
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We determined the role of chloride-bicarbonate anion exchanger 3 in formalin-induced acute and chronic rat nociception. Formalin (1%) produced acute (first phase) and tonic (second phase) nociceptive behaviors (flinching and licking/lifting) followed by long-lasting evoked secondary mechanical allodynia and hyperalgesia in both paws. Local peripheral pre-treatment with the chloride-bicarbonate anion exchanger inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid prevented formalin-induced nociception mainly during phase 2. ⋯ Furthermore, Western blot analysis revealed a band of about 85 kDa indicative of anion exchanger 3 protein expression in dorsal root ganglia of naïve rats, which was enhanced at 1 and 6 days after 1% formalin injection. On the other hand, this rise failed to occur during 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid exposure. These results suggest that anion exchanger 3 is present in dorsal root ganglia and participates in the development and maintenance of short and long-lasting formalin-induced nociception.
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Patients with osteoarthritis (OA) suffer from joint pain aggravated by movement, which affect their quality of life. In the present study, a weight bearing paradigm for pain at rest and a gait paradigm for pain during movement were tested in rats with unilateral knee arthritis induced by an intra-articular injection of sodium monoiodoacetate (MIA). At week 3 after MIA (1mg/knee) injection, animals developed pain-associated, right-left imbalances of weight distribution (weight bearing) or foot print parameters (gait). ⋯ We assessed the effect of different drugs on pain-induced disturbances in weight distribution and gait in MIA-induced arthritic rats. Analgesic drugs, each with different mechanisms of action, were less effective in rectifying the imbalance in gait than that in weight distribution. The assessment of the effect of analgesics on not only rest pain but pain during movement is valuable for the comprehensive examination of their therapeutic efficacies in OA.
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Reversing the respiratory depression induced by carfentanil involves intravenous administration of naloxone or naltrexone, but this treatment has disadvantages. Hence, finding a more appropriate treatment to counter the depressive actions of carfentanil is needed. In the present study, with the naloxone as a control, we investigated the efficacy of nalmefene for countering the depressive actions of carfentanil. ⋯ Furthermore, nalmefene (37.5-150.0 μg/kg) treatment could enable the PaO2, SaO2 and PaCO2 to approach normal levels 10 min (15 min after carfentanil injection) or 30 min (25 min after carfentanil injection) after injection. While, a single injection of naloxone (150.0 μg/kg, i.m.) only achieved partial remission of respiratory depression. These data suggest that nalmefene more effectively counters the depressive actions induced by carfentanil and is a more appropriate treatment to antagonize carfentanil toxicity compared with naloxone.
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Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. ⋯ Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.
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Milnacipran, a reuptake inhibitor of noradrenaline (NA) and serotonin (5-HT), elicits an antiallodynic effect in rats with neuropathic pain; however, the role of NA and 5-HT receptors in the induction of the antiallodynic effect of milnacipran remains unclear. Thus, we examined the effects of prazosin as an α1 adrenoceptor antagonist, yohimbine as an α2 adrenoceptor antagonist, metergoline as a 5-HT1, 5-HT2 and 5-HT7 receptor antagonist, cyanopindolol as a 5-HT1A/1B receptor antagonist, ketanserin as a 5-HT2 receptor antagonist, and ondansetoron as a 5-HT3 receptor antagonist on the antiallodynic effect of milnacipran in neuropathic rats with chronic constriction injury (CCI). The CCI rats expressed mechanical and thermal allodynia, which was attenuated by intrathecal injection of milnacipran. ⋯ Furthermore, c-Fos expression in lamina I/II of the spinal dorsal horn was enhanced by thermal stimulation and the enhanced expression of c-Fos was suppressed by milnacipran. This effect of milnacipran was reversed by yohimbine, metergoline, katanserin and ondansetron, but not prazosin. These results indicate that the effect of milnacipran on mechanical and thermal allodynia and c-Fos expression is elicited through the α2 adrenoceptor, but not α1 adrenoceptor, and 5-HT2 and 5-HT3 receptors; furthermore, the 5-HT1A/1B receptor is involved in mechanical allodynia, but not thermal allodynia.