European journal of pain : EJP
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Pain is a common and highly debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of multiple mechanisms including both inflammatory and neuropathic processes and also some unique changes. Strong opioids are a mainstay of treatments but side effects are problematic and can compromise optimal pain control. Tapentadol is a novel dual-action drug, both stimulating inhibitory μ-opioid receptors (MOR) and mediating noradrenaline reuptake inhibition (NRI) leading to activation of the inhibitory α-2 adrenoceptor. It has been demonstrated to treat effectively both acute and chronic pain. We here demonstrate the efficacy in a model of cancer-induced bone pain. ⋯ These findings add to the mechanistic understanding of cancer-induced bone pain and support the sparse clinical data indicating a possible use of the drug as a therapeutic alternative for cancer patients with metastatic pain complication.
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Previous studies have indicated that the startle reflex is potentiated by phasic, but not by tonic, heat pain, although the latter is seen as more strongly associated with emotional responses and more similar to clinical pain. The threat value of pain might be a decisive variable, which is not influenced alone by stimulus duration. ⋯ Our results suggest that subjective threat might indeed be decisive for the action of pain on startle; the threat level appears not only influenced by actual expectations but also by previous experiences with pain as threatening or not.
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Heterogeneity is increasingly recognized in clinical presentation of neuropathic pain (NP), but less often recognized in animal models. Neurochemical dysregulation in rodent dorsal root ganglia (DRG) is associated with peripheral nerve trauma, but poorly studied in non-traumatic NP conditions. ⋯ Taken together, the results suggest that ATF-3, GAP-43, NPY and galanin are likely indicators of nerve trauma-associated processes and not generic markers for NP. These experiments also demonstrate distinct expression patterns of neurochemical markers in the DRG and emphasize the mechanistic difference between nerve trauma and antiretroviral drug-associated NP.
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Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its underlying mechanisms remain elusive. Toll-like receptor 4 (TLR4) is a critical pattern recognition molecule of the innate immune system. In this study, we investigated whether the TLR4/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway in the spinal cord contributed to the visceral hypersensitivity induced by neonatal colonic irritation (CI) in rats. ⋯ These results suggest that neonatal CI stimulates the production of IL-1β and TNF-α through the TLR4/MyD88/NF-κB signalling pathway in the spinal cord, which contributed to visceral hypersensitivity induced by neonatal CI in rats.
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The application to the skin of spatially interlaced innocuous warm (40 °C) and cool (20 °C) thermodes (termed a thermal grill--TG) can produce an unusual thermal percept, but the mechanisms remain unclear. ⋯ The TG percept intensity and temporal profile were different from those evoked by either of its component parts. The perceived quality is person-specific. These differences suggest that the classic 'TG illusion' results from complex central integration of several types of peripheral afferent inputs activated by the TG. Differing body site-related roles of thermosensory afferents in discrimination versus temperature homeostasis may explain site-related variations in the percept.