Nalbuphine attenuates morphine-induced scratching by inhibiting PKCß-dependent microglial activation and p38 phosphorylation in male mice.

Morphine-induced scratching (MIS) is a common adverse effect associated with the use of morphine as analgesia after surgery. However, the treatment of MIS is less than satisfactory due to its unclear mechanism, which needs to be enunciated. We found that intrathecal (i.t.) injections of morphine significantly enhanced scratching behavior in C57BL/6J male mice as well as increased the expressions of protein kinase C ß (PKCß), phosphorylated p38 mitogen-activated protein kinases (MAPK), and ionized calcium-binding adapter molecule 1 (Iba1) within spinal cord dorsal horn. Conversely, using the kappa opioid receptor antagonist nalbuphine significantly attenuated scratching behavior, reduced PKCß expression and p38 phosphorylation, and decreased spinal dorsal horn microglial activation, while PKCδ and KOR expression elevated. Spinal PKCß silencing mitigated MIS and microglial activation. Still, knockdown of PKCδ reversed the inhibitory effect of nalbuphine on MIS and microglial activation, indicating that PKCδ is indispensable for the antipruritic effects of nalbuphine. In contrast, PKCß is crucial for inducing microglial activation in MIS in male mice. Our findings show a distinct itch cascade of morphine, PKCß/p38MAPK, and microglial activation, but an anti-MIS pathway of nalbuphine, PKCδ/KOR, and neuron activation.

Factors potentially associated with gemcitabine-based chemotherapy-induced thrombocytopenia in Chinese patients with nonsmall cell lung cancer.

OBJECTIVE: To investigate the prevalence and characteristics of gemcitabine-based chemotherapy-induced thrombocytopenia in Chinese patients with nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Medical records of 197 patients with histologically proven NSCLC received gemcitabine-based chemotherapy from June 2011 to June 2013 in our hospital were collected. The relative risk factors were identified and evaluated by univariate and multivariate analyses. RESULTS: The incidence of gemcitabine-based chemotherapy-induced thrombocytopenia in these NSCLC patients was 85.8%. Between thrombocytopenia and nonthrombocytopenia patients, in patients with thrombocytopenia and thrombocytopenia, we found Stage III/IV patients got more probabilities for thrombocytopenia (P < 0.01). In addition, patients who received gemcitabine and cisplatin (GP) regimen resulted in more thrombocytopenia than gemcitabine and carboplatin (GC) and other regimens (P < 0.001). In addition, majority of the thrombocytopenia patients presented thrombocytopenia in their first cycle (P < 0.001). Whereas, other potential risk factors such as age, gender, performance status value, diabetes mellitus or not, and other underlying disease (hypertension and hepatopathy) were not showed such significance in this study. Further, the multivariate analysis revealed that stage (odds ratio [OR] 7.113, P < 0.01) and chemotherapy cycles (OR 0.543, P < 0.01) were also statistically significant independent risk factors for gemcitabine-based chemotherapy-induced thrombocytopenia. CONCLUSION: This study shows that thrombocytopenia is common in Chinese NSCLC patients receiving gemcitabine-based regimens. Chemotherapy cycles and stage might be the important factors influencing the occurrence of gemcitabine-based regimens-induced thrombocytopenia.