Articles: neuralgia.
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The antineoplastic drugs cisplatin and vincristine induce peripheral neuropathies. The sigma-1 receptor (σ1R) is expressed in areas of pain control, and its blockade with the novel selective antagonist MR-309 has shown efficacy in nociceptive and neuropathic pain models. Our goal was to test whether this compound reduces neuropathic signs provoked by these antitumoural drugs. ⋯ σ1R antagonism could be an interesting and new option to palliate antitumoural neuropathies.
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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. ⋯ 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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Brain research bulletin · Mar 2019
Downregulated spinal IRF8 and BDNF in NAC are involved in neuropathic pain-induced depression relief via pulsed radiofrequency on dorsal root ganglion in rat SNI model.
Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG), which produces remarkable analgesia through high-frequency electromagnetic energy, has become a main therapy for chronic neuropathic pain. The chronic neuropathic pain in patients is frequently accompanied by depression. However, the underlying neurophysiological mechanisms of the treatment of PRF on DRG for the neuropathic pain-induced depression remain unclear. ⋯ Meanwhile, Western blot, immunohistochemistry, and RT-PCR revealed that PRF on DRG or intrathecal injection of IRF8 siRNA inhibited IRF8 overexpression in the spinal cord and brain-derived neurotrophic factor (BDNF) in NAc. These results suggest that neuropathic pain-induced depression could be attenuated by PRF applied to DRG in SNI rats. The suppressed overexpression of the spinal IRF8 and BDNF in NAc may play an important role and contribute considerably to effectiveness of the therapy by PRF on DRG.
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Naunyn Schmiedebergs Arch. Pharmacol. · Mar 2019
Etidronate attenuates tactile allodynia by spinal ATP release inhibition in mice with partial sciatic nerve ligation.
Etidronate is widely used as a therapeutic agent for osteoporosis. We have recently shown that intrathecal administration of etidronate into mice produces an analgesic effect against the capsaicin-induced nociceptive behavior. However, the effect of etidronate on neuropathic pain at the spinal level remains unknown. ⋯ SLC17A9 protein levels were also significantly increased. In mice subjected to PSNL, SLC17A9 was present in neurons and microglia, but not in astrocytes of the lumbar superficial dorsal horn. Collectively, our results suggest that etidronate produces its anti-allodynic effects by inhibiting SLC17A9-dependent exocytotic ATP release from the dorsal horn in mice subjected to PSNL.
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While as many as 60% of patients with spinal cord injury (SCI) develop chronic pain, limited data currently exists on the prevalence and profile of pain post-SCI in community dwelling populations. ⋯ Pain, in particular NP post SCI interferes with daily life, increases health service utilisation and remains refractory to current management strategies. Increased availability of multi-disciplinary pain management and further research into management strategies is warranted.