European journal of pain : EJP
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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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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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Mounting evidence points to individual contributions of tumour necrosis factor-alpha (TNF) and the c-Jun N-terminal kinase (JNK) pathway to the induction and maintenance of various pain states. Here we explore the role of spinal TNF and JNK in carrageenan-induced hypersensitivity. As links between TNF and JNK have been demonstrated in vitro, we investigated if TNF regulates spinal JNK activity in vivo. ⋯ Here we show that spinal JNK activity is dependent on TNF and that both TNF and the JNK signalling pathways modulate pain-like behaviour induced by peripheral inflammation.
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Previous studies have found an association between chronic pain and cardiovascular (CV) mortality. ⋯ A history of CV disease is reported more often in those with severe pain than would be expected by chance, even when adjusting for shared risk factors.