Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properties of Cav3 channels in superficial spinal dorsal horn. Our in vivo studies showed that the blockers of Cav3 channels robustly alleviated PSNL-induced mechanical allodynia and thermal hyperalgesia, which lasted at least 14 days following PSNL. Meanwhile, PSNL triggered an increase in both mRNA and protein levels of Cav3.2 but not Cav3.1 or Cav3.3 in rats. However, in Cav3.2 knockout mice, PSNL predominantly attenuated mechanical allodynia but not thermal hyperalgesia. In addition, the results of whole-cell patch-clamp recordings showed that both the overall proportion of Cav3 current-expressing neurons and the Cav3 current density in individual neurons were elevated in spinal lamina II neurons from PSNL rats, which could not be recapitulated in Cav3.2 knockout mice. Altogether, our findings reveal that the elevated functional Cav3.2 channels in superficial spinal dorsal horn may contribute to the mechanical allodynia in PSNL-induced neuropathic pain model.

Background Human papillomavirus (HPV) infection is associated with multiple types of cancer, but the evidence has not yet been fully elucidated in bladder cancer. Methods Frozen tissue samples collected from 146 patients aged 32 to 89 years-old with bladder cancer pathological diagnosis between 2015 and 2019 were analyzed. HPV genotyping and integration status determination were performed by capture-based next generation sequencing. Statistical analysis of HPV type distributions was performed according to stage, grade, gender and age group of patients. Results Mean age of 146 patients was 66.64 ± 10.06 years and 83.56% were male. Overall HPV infection rate was 28.77% (37.5% in female and 27% in male), with 11.90% HPV integration events. Among them, 17.12% single and 11.65% co-infections were observed. HPV18 (24.66%) was the most prevalent genotype, followed by HPV33, 16, 39. All HPV were European lineage (A). HPV16 was more prevalent in female (p=0.04). Conclusion HPV infection may contribute a causative role both in men and women with bladder cancer. HPV18, followed by HPV 33, 16 and 39 genotypes potentially represent the predominant oncogenic risk types of bladder carcinogenesis.

LXA(4) inhibited LPS-induced proliferation and reactive oxygen species production in RAW264.7 macrophages partially through modulation of G-CSF secretion.

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