European journal of pharmacology
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The analgesic properties of antidepressants are often used in the treatment of neuropathy; however their influence on glial cells in maintaining neuropathic pain is unknown. Our studies examined the neuropathic pain-relieving properties after intraperitoneal injection of amitriptyline, doxepin, milnacipran, venlafaxine and fluoxetine 7 days after sciatic nerve injury (CCI) in rats and its influence on microglia/macrophages (IBA-1) and astroglia (GFAP) activation in the spinal cord and dorsal root ganglia (DRG) using Western blot. All tested antidepressants significantly reduced CCI-induced allodynia but hyperalgesia was only antagonised by fluoxetine, doxepine and venlafaxine. ⋯ No changes in the GFAP level in both structures were observed after any of listed above antidepressants administration. Chronic minocycline treatment enhanced amitriptyline and milnacipran, but did not fluoxetine analgesia under neuropathic pain in rats. Our results suggest that nerve injury-induced pain is related with the activation of microglia, which is diminished by fluoxetine treatment in the neuropathic pain model.
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Granulocyte-colony stimulating factor (G-CSF) is a therapeutic approach to increase peripheral neutrophil counts after anti-tumor therapies. Pain is the major side effect of G-CSF. Intraplantar administration of G-CSF in mice induces mechanical hyperalgesia. ⋯ Systemic IL-1ra reduced G-CSF-induced increase of peripheral neutrophil counts. However, local treatment with morphine, IL-1ra or etanercept, and systemic treatment with indomethacin, etanercept, thalidomide and pentoxifylline did not alter G-CSF-induced mobilization of neutrophils. Therefore, this study advances in the understanding of G-CSF-induced hyperalgesia and suggests therapeutic approaches for its control.
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Treatments for neuropathic pain are either not fully effective or have problematic side effects. Combinations of drugs are often used. Tapentadol is a newer molecule that produces analgesia in various pain models through two inhibitory mechanisms, namely central μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition. ⋯ Systemic tapentadol resulted in dose-dependent decrease in right CeA neuronal activity only in neuropathy. Both naloxone and yohimbine reversed this effect to an extent that was modality selective. The interactions of the components of tapentadol are not limited to the synergy between the MOR and α2-adrenoceptors seen at spinal levels, but are seen at this supraspinal site where suppression of responses may relate to the ability of the drug to alter affective components of pain.
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Endotoxemia induces various physiological adaptive responses such as tachycardia. There is evidence to show that inflammatory tachycardia might be linked to a direct action of prostanoids on the cardiac pacemaker cells. Recent reports have indicated that systemic inflammation may uncouple of cardiac pacemaker from cholinergic neural control in experimental animals; however, the exact mechanism of this phenomenon is uncertain. ⋯ Incubation with prostaglandin F₂α (PGF₂α, 100 pM) could significantly decrease chronotropic response to cholinergic stimulation in vitro. Likewise, LPS injection could induce a significant hyporesponsiveness to cholinergic stimulation, and incubation of isolated atria with either indomethacin (5 µM) or AL-8810 (a PGF₂α antagonist, 10 µM) could reverse it (P<0.01, P<0.05, respectively), while SQ29548 (a thromboxane A₂ antagonist, 10 nM) was failed (P>0.05). Our data showed that PGF₂α may contribute to the atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats.
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Caesalpinia sappan L. (Lignum Sappan) is a Chinese medicinal plant for treating ischemic cerebral apoplexy. Deoxysappanone B (DSB), a homoisoflavone compound isolated from C. sappan L. (Lignum Sappan), was studied for anti-neuroinflammatory and neuroprotective properties using lipopolysaccharide (LPS)-induced BV-2 microglia neuroinflammation model and LPS-induced microglia-neuron co-culture system. Our findings showed that DSB effectively inhibited BV-2 microglia-mediated neuroinflammatory mediators׳ release including NO, PGE₂, TNF-α, IL-6 and reactive oxygen species. ⋯ Mechanism study revealed that DSB blocked two major neuroinflammation-related signaling pathways including IKK-IκB-nuclear factor kappaB (NF-κB) and p38/ERK mitogen-activated protein kinase (MAPK) cascades, further leading to the inhibition of neuroinflammatory mediators׳ production. The present study provides evidence that the anti-neuroinflammatory and neuroprotective effect of DSB are due to the suppression of neuroinflammatory mediators׳ production as well as inflammation-induced neurotoxicity through regulation of multi-targets. Therefore, DSB may serve as a neuroprotective agent for the treatment of neuroinflammatory disorders and inflammation-related neuronal injury.