Plos One
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Since accumulating evidence suggests the application of anesthetics may increase the risk of Alzheimer's disease (AD), we investigated the cytotoxicity of inhaled general anesthesia in neurons and its underlying mechanism. Using primary cultured rat hippocampal neurons as the study model, here we show that isoflurane increases vulnerability to intracellular or extracellular amyloid β with or without serum deprivation. ⋯ We conclude that isoflurane increases cell death in the presence of amyloid β by increasing Bax level through downregulating miR-214. Our data provide a new insight for inhaled anesthetics toxicity and indicate a possible mechanistic link between anesthetic application and neurodegenration in AD.
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Substance P (SP) and its receptor, the neurokinin 1 receptor (NK1R), play important roles in transmitting and regulating somatosensory nociceptive information. However, their roles in visceral nociceptive transmission and regulation remain to be elucidated. In the previous study, moderate SP immunoreactive (SP-ir) terminals and NK1R-ir neurons were observed in the dorsal commissural nucleus (DCN) of the lumbosacral spinal cord. ⋯ Meanwhile, formalin instillation induced a biphasic visceral pain response as well as a strong expression of Fos protein in the nuclei of neurons in the DCN. Finally, intrathecal treatment with the NK1R antagonist L732138 attenuated the NK1R internalization, Fos expression and visceral nociceptive responses. The present results suggest that the visceral nociceptive information arising from inflamed pelvic organs, such as the lower colon, might be mediated by the NK1R-ir neurons in the DCN of the lumbosacral spinal cord.
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Unaccustomed strenuous exercise that includes lengthening contraction (LC) often causes tenderness and movement related pain after some delay (delayed-onset muscle soreness, DOMS). We previously demonstrated that nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) are up-regulated in exercised muscle through up-regulation of cyclooxygenase (COX)-2, and they sensitized nociceptors resulting in mechanical hyperalgesia. There is also a study showing that transient receptor potential (TRP) ion channels are involved in DOMS. ⋯ Expression of NGF and COX-2 mRNA was significantly increased 3 h after LC in all genotypes. However, GDNF mRNA did not increase in TRPV4-/- mice. These results suggest that TRPV1 contributes to DOMS downstream (possibly at nociceptors) of NGF and GDNF, while TRPV4 is located downstream of GDNF and possibly also in the process of GDNF up-regulation.
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Simvastatin exerts pleiotropic effects on cardiovascular system. However, its effect on non-alcoholic fatty liver disease, especially the liver fibrosis, remains obscure. We aimed to clarify the relationship between simvastatin and liver fibrosis both in vivo and in vitro. ⋯ Simvastatin improves the prognosis of NASH-related fibrosis by increasing the expression of eNOS, decreasing the expression of iNOS, and inhibiting the activation of HSC.
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Oxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission. ⋯ A polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity.