Inhibition of interleukin-6 function attenuates the central sensitization and pain behavior induced by osteoarthritis.

Chronic pain is the most prominent and disabling symptom in the patients with osteoarthritis (OA), and the underlying mechanism largely remains unclear. Interleukin-6 (IL-6), a proinflammatory cytokine, is critically involved in the development and maintenance of central sensitization in several rodent models of chronic pain. The present study aims to elucidate the IL-6 mediated neurological adaptation in dorsal horn in the rat with monosodium iodoacetate (MIA) - induced OA. Significant upregulation of IL-6 expression was detected in the dorsal horn in the modeled rats. Blockade of IL-6 function by tocilizumab markedly suppressed the activation of astrocytes and microglia in the ipsilateral dorsal horn, reduced c-Fos immunoreactivity in dorsal horn neurons, and attenuated the upregulation of glutamate receptor subunits GluR1 and NR2B in dorsal horn in the rats with MIA-induced OA. It was further reported that administration of tocilizumab significantly improved the performance in weight-bearing test and mitigated the mechanical allodynia in the modeled rats. These data illustrated spinal IL-6 mediated mechanism underlying the chronic pain, and proposed the potential therapeutic effect of tocilizumab on the chronic pain in the setting of OA.

[Effects of Tramadol on Insulin Resistance during Cesarean Section Complicated with Gestational Diabetes Mellitus].

OBJECTIVES: To investigate the effects of tramadol on insulin resistance (IR) during cesarean section complicated with gestational diabetes mellitus (GDM). METHODS: 120 patients of elective caesarean sectioncomplicated with GDM (level A1) were collected from Dec.2015 to Oct.2016, randomly divided into the tramadol injection treated groups (0.5 mg/kg-TRM1, 1 mg/kg-TRM2 and 1.5 mg/kg-TRM3) and the control group (CON) (n=30). The patients of TRM groups were injected with tramadol after delivery of fetus during caesarean delivery under combined spinal-epidural anaesthesia (CSEA) and the patients of CON group were treated with normal saline as control. The plasma were collected before CSEA (T0), after delivery of fetus (T1) and immediately after caesarean section (T2) for determination of the expression of blood glucose, insulin, HOMA-IR, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by hexokinase, chemiluminescence method and ELISA. The activation of PI3K/Akt signaling pathway of epiploon were detected by RT-PCR and Western blot. RESULTS: Compared with T0, the concentration of blood glucose, insulin, HOMA-IR, IL-6 and TNF-α increased significantly in T1 and T2 (P<0.05). The factors of above decreased in T2 of TRM2 group and TRM3 group comparing with CON group, but of no significant differences between TRM1 group and CON group. Compared with CON group in T2, PI3K/Akt signaling pathway activated significantly in TRM2 group and TRM3 group (P<0.05). CONCLUSIONS: The tramadol can attenuate IR during cesarean section complicated with GDM and may regulate the secretion of IL-6, TNF-α and PI3K/Akt signaling pathway in the treatment of IR of GDM.

[Protective Effect of Activated Nrf2 against Hyperoxia-induced Lung Injury in Neonatal Rats].

OBJECTIVE: To observe the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) agonist on the apoptosis of alveolar cell induced by hyperoxia and to explore whether Nrf2 activation could protect neonatal rats from hyperoxia induced lung injury. METHODS: 90 neonatal Sprague-Dawley rats were randomized into room air group (FiO2 =21%, N group), hyperoxia group (0 group) and Nrf2 group (n=30 each). Neonatal rats in the 0 group and Nrf2 group received saline 0. 2 mL and Nrf2 agonist 30 mg/kg respectively at the first and second day after birth, and were exposed in high concentration oxygen (95%) for 4 d. N group rats were fed in room air. The apoptotic index (AI) and Nrf2 expression of lung tissue were detected by TUNEL and immunohistochemistry staining respectively. RESULTS: Compared with 0 group (28. 8% ± 3. 0%), the AI of alveolar. cell was lower in N group (0. 7%±0. 6%) and Nrf2 group (7. 2% ± 0. 8%) (P<0. 01). The expression of Nrf2 was significantly higher in 0 group (926. 80 ± 130. 51) and Nrf2 group (1038. 40±151. 12) than that in N group (30. 03±9. 99) (P<0. 01). CONCLUSION: Nrf2 activation could reduce the alveolar cellular apoptosis and protect neonatal rats from hyperoxia induced lung injury.