Expression of acetylated histone 3 in the spinal cord and the effect of morphine on inflammatory pain in rats

In this study, a rat model of inflammatory pain was produced by injecting complete Freund’s adjuvant into the hind paw, and the expression of acetylated histone 3 in the spinal cord dorsal horn was examined using immunohistochemical staining. One day following injection, there was a dramatic decrease in acetylated histone 3 expression in spinal cord dorsal horn neurons. However, on day 7, expression recovered in adjuvant-injected rats. While acetylated histone 3 labeling was present in dorsal horn neurons, it was more abundant in astrocytes and microglial cells. The recovery of acetylated histone 3 expression was associated with a shift in expression of the protein from neurons to glial cells. Morphine injection significantly upregulated the expression of acetylated histone 3 in spinal cord dorsal horn neurons and glial cells 1 day after injection, especially in astrocytes, preventing the transient downregulation. Our results indicate that inflammatory pain induces a transient downregulation of acetylated histone 3 in the spinal cord dorsal horn at an early stage following adjuvant injection, and that this effect can be reversed by morphine. Thus, the downregulation of acetylated histone 3 may be involved in the development of inflammatory pain.

ProBDNF Acts as an Angiogenesis Inhibitor

Brain-derived neurotrophic factor (BDNF) has been considered a new angiogenesis mediator. ProBDNF, the precursor of BDNF, plays opposite neuronal functions to BDNF, but the role of proBDNF on angiogenesis remains unknown. We found human umbilical vein endothelial cells (HUVEC) expressing BDNF, proBDNF, p75NTR, Sortilin and TrkB. ProBDNF significantly decreased HUVEC viability in MTT assay, and this inhibition was neutralized by anti-proBDNF. Endothelial cell tube formation assay showed that proBDNF significantly inhibits HUVEC angiogenesis in vitro. Matrigel plug assay disclosed that proBDNF also impeded angiogenesis in vivo, while anti-proBDNF greatly facilitated angiogenesis. Immunostaining of CD31 and α-SMA in Matrigel plugs confirmed the inhibitive effect of proBDNF on angiogenesis. In conclusion, proBDNF can act as an angiogenesis inhibitor. It added more evidence to the “Yin-Yang” theory by showing mBDNF is a mediator of angiogenesis as “Yang” and proBDNF works as an angiogenesis inhibitor as “Yin”.