Taselisib moderates neuropathic pain through PI3K/AKT signaling pathway in a rat model of chronic constriction injury.

BACKGROUND: Neuropathic pain is a chronic condition commonly caused by inflammation-induced disturbances or lesions of somatosensory functions in the nervous system. The aim of this study was to investigate the effects and mechanisms of Taselisib on chronic constriction injury (CCI)-induced neuropathic pain in rats. METHODS: The rats were divided into four groups: sham group, sham + Taselisib (10 mg/kg orally once a day) group, CCI group, and CCI + Taselisib (10 mg/kg orally once a day) group. Pain behavioral tests, recorded by measuring paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL), were conducted on days 0, 3, 7, 14, and 21 after surgery. After testing, the animals were euthanized and spinal dorsal horns were collected. Pro-inflammatory cytokines were quantified using ELISA and qRT-PCR. PI3K/pAKT signaling was assessed using Western blot and immunofluorescence. RESULTS: PWT and TWL were significantly reduced after CCI surgery, but were successfully increased by Taselisib treatment. Taselisib treatment notably suppressed the upregulation of pro-inflammatory cytokines, including IL-6, IL-1ß, and TNF-⍺. Taselisib treatment significantly reduced the elevated phosphorylation of AKT and PI3K induced by CCI. CONCLUSION: Taselisib can alleviate neuropathic pain by inhibiting the pro-inflammatory response, potentially through the PI3K/AKT signaling pathway.

The effect of phosphodiesterase isoenzyme 5 inhibitors on ureteropelvic junction obstruction in rabbits.

OBJECTIVE: To determine the effects of phosphodiesterase isoenzyme 5 (PDE5) inhibitors upon ureteropelvic junction obstruction (UPJO) in rabbits. MATERIALS AND METHODS: Twenty-four New Zealand rabbits were randomly divided into three groups: sham-operated animals (group A; right-sided operations comprised subgroup A1 and left-sided operations comprised subgroup A2), operated animals (group B) and operated animals that received vardenafil (group C). The right-sided junctions of group A (A1) were not exposed, and therefore made up the control group. The UPJO model was established by partial obstruction of the left junction. Intravenous pyelograms were performed before and after the operation. HE staining and microscopic examinations were performed to chart the pathological changes. Immunohistochemistry (streptavidin peroxidase) was used to test the expression of TGF-beta1 and nNOS in the junctions. RT-PCR detected mRNA expression of TGF-beta1. RESULTS: We observed serious hydronephrosis in group B and moderate hydronephrosis in group C, but not in group A. We also observed large pathological changes in group B, but little change in group C and no change in subgroups A1 and A2. The level of TGF-beta1 in group B was significantly higher than in groups A and C; group C expressed more TGF-beta1 than group A. More nNOS was detected in group C than group B, although the two groups both expressed nNOS at lower levels than group A. CONCLUSIONS: More TGF-beta1 and less nNOS are expressed when the junction is obstructed. PDE5 inhibitors may be able to regulate these 2 factors, or other factors that have not been discussed in this experiment, in order to halt the progression of UPJO.