Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Aug 2015
Meta AnalysisEfficacy of perioperative dexmedetomidine in postoperative neurocognitive function: a meta-analysis.
Neuroprotective effects of dexmedetomidine are reported in preclinical and clinical studies but evidence regarding the postoperative neurocognitive function is not as clear. This study performed a meta-analysis on outcomes of studies which examined neurocognitive performance by using valid assessment tools before and after perioperative dexmedetomidine treatment. Literature was searched in several electronic databases and studies were selected by following précised inclusion criteria. ⋯ Perioperative dexmedetomidine treatment was associated with significantly better neurocognitive performance in comparison with saline (mean difference (95% CI): 9.10 (3.03, 15.16) %; P = 0.003) as well as with comparator anaesthetics (mean difference: 5.50 (0.15, 10.86) %; P = 0.04) treated patients. In the submeta-analyses of studies which utilized neurocognitive assessment tools other than Mini-Mental State Examination (mean difference: 6.66 (-3.42, 16.74); P = 0.20) or studies with patients under 60 years of age (mean difference: 7.48 (-3.00, 17.96); P = 0.16), the differences were not significant between dexmedetomidine- and saline-/comparator-treated patients. Perioperative dexmedetomidine treatment is associated with significantly better neurocognitive function postoperatively in comparison with both saline controls and comparator anaesthetics (predominantly midazolam).
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Clin. Exp. Pharmacol. Physiol. · Aug 2015
Meta AnalysisEffect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta-analysis.
This study examined the effects of perioperative dexmedetomidine treatment on physiological modulators of surgical stress response. The quality of the included studies was assessed prior to performing meta-analyses of the weighted mean differences in the changes from baseline of stress hormones and interpreted in the light of statistical heterogeneity between the studies. Nineteen studies (844 surgical subjects) data were used for this meta-analysis. ⋯ Dexmedetomidine also decreased prolactin levels with a mean difference of -19.42 (-39.37, 0.52) μg/L (P = 0.06). In conclusion, perioperative use of dexmedetomidine reduces serum catecholamine and cortisol levels but the decrease in cortisol levels was not statistically different from the comparator anaesthetics. More data will be required to assess the effects of dexmedetomidine on corticotropin, prolactin, and growth hormone.
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Clin. Exp. Pharmacol. Physiol. · Jul 2015
Clinical TrialThe Dynamic cerebral autoregulatory adaptive response to noradrenaline is attenuated during systemic inflammation in humans.
Vasopressor support is used widely for maintaining vital organ perfusion pressure in septic shock, with implications for dynamic cerebral autoregulation (dCA). This study investigated whether a noradrenaline-induced steady state increase in mean arterial blood pressure (MAP) would enhance dCA following lipopolysaccharide (LPS) infusion, a human-experimental model of the systemic inflammatory response during early sepsis. The dCA in eight healthy males was examined prior to and during an intended noradrenaline-induced MAP increase of approximately 30 mmHg. ⋯ After LPS, noradrenaline administration changed neither gain (0.91 (0.85-1.01) vs 0.87 (0.81-0.97) cm/mmHg per s; P = 0.46) nor phase (1.10 (1.04-1.30) vs 1.37 (1.23-1.51) radians; P = 0.64). The improvement of dCA to a steady state increase in MAP is attenuated during an LPS-induced systemic inflammatory response. This may suggest that vasopressor treatment with noradrenaline offers no additional neuroprotective effect by enhancing dCA in patients with early sepsis.
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Clin. Exp. Pharmacol. Physiol. · Jul 2015
Effects of intermedin on dorsal root ganglia in the transmission of neuropathic pain in chronic constriction injury rats.
Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. The P2X3 receptor plays a crucial role in facilitating pain transmission. Intermedin (IMD), which is also known as adrenomedullin 2 (AMD2) is a newly discovered hormone that is a member of the calcitonin/calcitonin gene-related peptide family. ⋯ The phosphorylation of p38 and ERK1/2 in L4/L5 DRG in the CCI+NS group and the CCI+IMD1-53 group was stronger than that in the Control group or the Sham group; however, the phosphorylation of p38 and ERK1/2 in the CCI+IMD14-47 group was much lower than that in the CCI+NS group or the CCI+IMD1-53 group. Our findings indicate that IMD might increase the sensitization effects of IMD on P2X3 receptors to alleviate chronic neuropathic pain injury. The IMD agonist IMD1-53 might enhance nociceptive responses mediated by P2X3 receptors in neuropathic pain, and the IMD inhibitor IMD14-47 could inhibit the sensitization of the P2X3 receptor in chronic neuropathic pain injury.
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Clin. Exp. Pharmacol. Physiol. · Jul 2015
Inhibition of microglial activity alters spinal wide dynamic range neuron discharge and reduces microglial Toll-like receptor 4 expression in neuropathic rats.
It is believed that neuropathic pain results from aberrant neuronal discharges although some evidence suggests that the activation of glia cells contributes to pain after an injury to the nervous system. This study aimed to evaluate the role of microglial activation on the hyper-responsiveness of wide dynamic range neurons (WDR) and Toll-like receptor 4 (TLR4) expressions in a chronic constriction injury (CCI) model of neuropathic pain in rats. Adult male Wistar rats (230 ± 30 g) underwent surgery for induction of CCI neuropathy. ⋯ Post-injury administration of minocycline effectively decreased thermal hyperalgesia, TLR4 expression, and hyper-responsiveness of WDR neurons in CCI rats. The results of this study indicate that post-injury, repeated administration of minocycline attenuated neuropathic pain by suppressing microglia activation and reducing WDR neuron hyper-responsiveness. This study confirms that post-injury modulation of microglial activity is a new strategy for treating neuropathic pain.