Scientific reports
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We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. ⋯ Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.
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Sirtuin 3 (SIRT3) is the main mitochondrial deacetylase. SIRT3 regulates cell metabolism and redox homeostasis, and protects from aging and age-associated pathologies. SIRT3 may drive both oncogenic and tumor-suppressive effects. ⋯ Using SIRT3 knockout mice, we show that SIRT3 deficiency does not affect immune cell development and microbial ligand-induced proliferation and cytokine production by splenocytes, macrophages and dendritic cells. Going well along with these observations, SIRT3 deficiency has no major impact on cytokine production, bacterial burden and survival of mice subjected to endotoxemia, Escherichia coli peritonitis, Klebsiella pneumoniae pneumonia, listeriosis and candidiasis of diverse severity. These data suggest that SIRT3 is not critical to fight infections and support the safety of SIRT3-directed therapies based on SIRT3 activators or inhibitors for treating metabolic, oncologic and neurodegenerative diseases without putting patients at risk of infection.
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Danish nationwide registries were used to investigate temporal trends in initiation of rivaroxaban or apixaban or dabigatran versus vitamin K antagonists (VKA) in patients with venous thromboembolism (VTE). Patients treated with one of the NOACs (rivaroxaban, dabigatran, apixaban) or VKA were identified between February 2012 and September 2016. A total of 19,578 patients were included of which 10,844 (55.4%) were treated with VKA and 8,734 (44.6%) were treated with NOACs (rivaroxaban 7,572, apixaban 1,066, and dabigatran 96). ⋯ Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with one of the NOACs. In conclusion the initiation of rivaroxaban and apixaban is increasing significantly over time in patients with VTE. Patients with previous VTE, chronic kidney disease, liver disease, cancer, and thrombophilia were more likely to be initiated on VKA compared with rivaroxaban or apixaban.
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Acupuncture is an alternative treatment for wide spectrum chronic pain. However, its validity remains controversial due to the disputed efficacy assessed in various clinical studies. Moreover, variability amongst individuals complicates the predictability of outcome, which impedes the integration of acupuncture into mainstream pain management programs. ⋯ Local administration of caffeine at the acupuncture point was sufficient to eliminate the analgesic effect, dismissing the systemic action of caffeine. Such interference was reversible, as caffeine withdrawal fully restored the efficacy of acupuncture by the next day, and long-term exposure to caffeine did not alter A1 receptor expression at the acupuncture point. Combined, these data indicate that a trace amount of caffeine can reversibly block the analgesic effects of acupuncture, and controlling caffeine consumption during acupuncture may improve pain management outcomes.
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The human ability to synchronize with other individuals is critical for the development of social behavior. Recent research has shown that physiological inter-personal synchronization may underlie behavioral synchrony. Nevertheless, the factors that modulate physiological coupling are still largely unknown. ⋯ Critically, we found that high partner's empathy and high levels of analgesia enhanced coupling during the partner's touch. Collectively, the evidence indicates that social touch increases interpersonal physiological coupling during pain. Furthermore, the effects of touch on cardio-respiratory inter-partner coupling may contribute to the analgesic effects of touch via the autonomic nervous system.