The possible involvement of JNK activation in the spinal dorsal horn in bortezomib-induced allodynia: the role of TNF-α and IL-1ß.

PURPOSE: Bortezomib (BTZ), a widely used chemotherapeutic drug, is closely associated with the development of painful peripheral neuropathy, but the mechanism underlying the induction of this disorder by BTZ remains largely unclear. To examine this association, we have evaluated the activation of mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn and the role of tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) in BTZ-induced allodynia in rats. METHODS: Male Sprague-Dawley rats were used as the model animals. The paw withdrawal test, in which mechanical stimuli (von Frey hairs) is applied to the plantar surface of the hindpaw, was used to determine any changes in the paw withdrawal threshold of the treated rats. A PE-10 catheter was placed intrathecally to deliver TNF-α neutralizing antibody, IL-1 receptor antagonist (IL-1ra) or the c-Jun N-terminal kinase (JNK) inhibitor SP600125. The mRNA levels of various cytokines were measured by real-time quantitative PCR. The expression of TNF-α, IL-1ß and mitogen-activated protein kinase (MAPK) family members in the spinal dorsal horn was measured by western blot analysis and immunohistochemistry. All data were expressed as the mean ± standard error of the mean and analyzed using the SPSS version 13.0 software program. RESULTS: The BTZ treatment induced an upsurge in the mRNA and protein levels of TNF-α in the neurons and IL-1ß in the astrocytes in the spinal dorsal horn. It also significantly upregulated the phosphorylation of JNK but not of extracellular signal-regulated kinases (ERK) and p38-MAPK in astrocytes of the spinal dorsal horn. Inhibition of TNF-α or IL-1ß ameliorated JNK activation and mechanical allodynia induced by BTZ. Co-administration of thalidomide (TNF-α synthesis inhibitor) and IL-1ra prevented BTZ-induced mechanical allodynia. CONCLUSION: Our results suggest that the TNF-α or IL-1ß/JNK pathway in the spinal dorsal horn may play a critical role in the development of painful peripheral neuropathy induced by BTZ.

[Effects of irrigation amount on leaf structure, photosynthetic physiology, and fruit yield of Lycium barbarum in arid area].

Lycium barbarum is an important traditional medicinal plant in China. Under controlled condition, a field experiment was conducted to study the effects of different monthly irrigation quota on the leaf structure, photosynthetic physiology, and fruit yield of L. barbarum, aimed to determine an appropriate irrigation amount for the plant. When the monthly irrigation quota was less than 900 m3 x hm(-2), the leaf area, leaf thickness, palisade tissue thickness, cell tense ratio (CTR), net photosynthetic rate (Pn), intrinsic water use efficiency (WUE), stomatal limitation value (Ls), and fruit yield of L. barbarum all increased significantly with monthly irrigation quota, while leaf stoma density and intercellular CO2 concentration (Ci) showed a reverse trend. When the irrigation quota was more than 900 m3 x hm(-2), the Ci increased with irrigation quota, the leaf area, stoma density, and fruit yield had no obvious change, whereas the other indices showed a reverse trend. The leaf transpiration rate and Gs were the highest at irrigation quota 450 m3 x hm(-2), being 8.02 and 324 mmol x m(-2) x s(-1), respectively; whereas at other irrigation quota, these two indices were lower than the control. In terms of saving water, the monthly irrigation quota 900 m3 x hm(-2) was more appropriate for Lycium barbarum.