X-ray induces mechanical and heat allodynia in mouse via TRPA1 and TRPV1 activation.

Radiotherapy-related pain is a common adverse reaction with a high incidence among cancer patients undergoing radiotherapy and remarkably reduces the quality of life. However, the mechanisms of ionizing radiation-induced pain are largely unknown. In this study, mice were treated with 20 Gy X-ray to establish ionizing radiation-induced pain model. X-ray evoked a prolonged mechanical, heat, and cold allodynia in mice. Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 were significantly upregulated in lumbar dorsal root ganglion. The mechanical and heat allodynia could be transiently reverted by intrathecal injection of transient receptor potential vanilloid 1 antagonist capsazepine and transient receptor potential ankyrin 1 antagonist HC-030031. Additionally, the phosphorylated extracellular regulated protein kinases (ERK) and Jun NH2-terminal Kinase (JNK) in pain neural pathway were induced by X-ray treatment. Our findings indicated that activation of transient receptor potential ankyrin 1 and transient receptor potential vanilloid 1 is essential for the development of X-ray-induced allodynia. Furthermore, our findings suggest that targeting on transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 may be promising prevention strategies for X-ray-induced allodynia in clinical practice.

Comparative study of duloxetine pharmacokinetics in normal and diabetic rats / 药学学报

The study was aimed to establish a liquid chromatography-tandem mass spectrometric method for the determination of the duloxetine concentration in rat plasma, and compare the pharmacokinetics in normal and diabetes mellitus rat models. Diazepam was used as an internal standard. The separation was achieved on a Waters Xterra® RP18 column (100 mm × 4.6 mm, 3.5 μm) with a mobile phase consisting of methanol -0.3% formic acid containing 5 mmol·L-1 ammonium acetate (75:25) at the flow rate of 0.6 mL·min-1. Electrospray ionization source was applied and operated in the positive multiple reaction monitoring mode. A good linearity of duloxetine was obtained in the concentration range of 10-5 000 ng·mL-1. The rat models of diabetes mellitus were established by intraperitoneal injection of streptozotocin. The same dose of duloxetine (40 mg·kg-1) was given by intragastric administration to the normal and diabetic rats. Blood samples were collected from the orbital venous plexus to determinate duloxetine concentration in the plasma. The pharmacokinetic parameters were calculated by DAS software. Statistical analysis was performed by SPSS software. The major pharma-cokinetic parameters of diabetes group were as follows: Cmax was 1 185 ± 190.0 ng·mL-1; AUC0-∞ was 8 398 ± 1 835 ng·mL-1·h; tmax was 1.6 ± 0.4 h; t1/2z was 3.6 ± 0.9 h. The major pharmacokinetic parameters of normal group were as follows: Cmax was 368.1 ± 40.7 ng·mL-1; AUC0-∞ was 4145 ± 640.1 ng·mL-1·h; tmax was 1.6 ± 0.3 h; t1/2z was 4.1 ± 0.8 h. The results of pharmacokinetic experiments suggest that the exposure amount of duloxetine in diabetic rats is twice higher than that in normal rats.