Painful peripheral neuropathy is a dose-limiting side effect of cisplatin treatment. Using a murine model of cisplatin-induced hyperalgesia, we determined whether a PPARγ synthetic agonist, pioglitazone, attenuated the development of neuropathic pain and identified underlying mechanisms. Cisplatin produced mechanical and cold hyperalgesia and decreased electrical thresholds of Aδ and C fibers, which were attenuated by coadministration of pioglitazone (10 mg/kg, intraperitoneally [i.p.]) with cisplatin. Antihyperalgesic effects of pioglitazone were blocked by the PPARγ antagonist T0070907 (10 mg/kg, i.p.). We hypothesized that the ability of pioglitazone to reduce the accumulation of reactive oxygen species (ROS) in dorsal root ganglion (DRG) neurons contributed to its antihyperalgesic activity. Effects of cisplatin and pioglitazone on somatosensory neurons were studied on dissociated mouse DRG neurons after 24 hours in vitro. Incubation of DRG neurons with cisplatin (13 µM) for 24 hours increased the occurrence of depolarization-evoked calcium transients, and these were normalized by coincubation with pioglitazone (10 µM). Oxidative stress in DRG neurons was considered a significant contributor to cisplatin-evoked hyperalgesia because a ROS scavenger attenuated hyperalgesia and normalized the evoked calcium responses when cotreated with cisplatin. Pioglitazone increased the expression and activity of ROS-reducing enzymes in DRG and normalized cisplatin-evoked changes in oxidative stress and labeling of mitochondria with the dye MitoTracker Deep Red, indicating that the antihyperalgesic effects of pioglitazone were attributed to its antioxidant properties in DRG neurons. These data demonstrate clear benefits of broadening the use of the antidiabetic drug pioglitazone, or other PPARγ agonists, to minimize the development of cisplatin-induced painful neuropathy.

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Prescription opioid medications continue to be abused on an epidemic level and have been shown to be a "gateway" drug to heroin abuse. Individuals experimenting with opioids commonly fall in the 10- to 19-year age range in which dentists are the highest prescribers. To reduce the number of excess opioids, the Department of Oral and Maxillofacial Surgery, University of Minnesota, developed and implemented an evidence-based opioid prescribing policy. Data were collected via electronic health record for the previous year and compared with the year following the protocol implementation. The results showed a drastic decrease (>46%) in the number of prescriptions given over a 1-year period. All departments reported a decrease in opioid prescriptions and the average number of tablets per prescription. The concern of undertreating pain was not found to be significant, as there was no increase in after-hours calls, recall appointments, or documentable emergency room visits. The results support the efficacy of an opioid prescribing policy's ability to lower the frequency and number of opioids given to patients, while still adequately treating patients' pain. Continued evaluation and modifications of the protocol and close monitoring of prescriber habits will enhance patients' pain control while also limiting the number of opioids available for abuse.

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