The natural product argentatin C attenuates postoperative pain via inhibition of voltage-gated sodium and T-type voltage-gated calcium channels.

BACKGROUND AND PURPOSE: Postoperative pain occurs in as many as 70% of surgeries performed worldwide. Postoperative pain management still relies on opioids despite their negative consequences, resulting in a public health crisis. Therefore, it is important to develop alternative therapies to treat chronic pain. Natural products derived from medicinal plants are potential sources of novel biologically active compounds for development of safe analgesics. In this study, we screened a library of natural products to identify small molecules that target the activity of voltage-gated sodium and calcium channels that have important roles in nociceptive sensory processing. EXPERIMENTAL APPROACH: Fractions derived from the Native American medicinal plant, Parthenium incanum, were assessed using depolarization-evoked calcium influx in rat dorsal root ganglion (DRG) neurons. Further separation of these fractions yielded a cycloartane-type triterpene identified as argentatin C, which was additionally evaluated using whole-cell voltage and current-clamp electrophysiology, and behavioural analysis in a mouse model of postsurgical pain. KEY RESULTS: Argentatin C blocked the activity of both voltage-gated sodium and low-voltage-activated (LVA) calcium channels in calcium imaging assays. Docking analysis predicted that argentatin C may bind to NaV 1.7-1.9 and CaV 3.1-3.3 channels. Furthermore, argentatin C decreased Na+ and T-type Ca2+ currents as well as excitability in rat and macaque DRG neurons, and reversed mechanical allodynia in a mouse model of postsurgical pain. CONCLUSION AND IMPLICATIONS: These results suggest that the dual effect of argentatin C on voltage-gated sodium and calcium channels supports its potential as a novel treatment for painful conditions.

Alumina nanoparticles alter rhythmic activities of local interneurons in the antennal lobe of Drosophila.

The special physical and chemical properties of nanomaterials open up new capabilities and functions. However, concerns have been raised about the risks produced by nanoparticles, their potential to cause undesirable effects, such as contamination of the environment and other adverse effects. In this study, we used Drosophila as a model organism to explore the effects of nano-alumina on the central nervous system. We focused on the rhythmic activities in the antennal lobe of Drosophila using patch clamps to record the electrophysiological activities. We found that 15 min after application of alumina nanoparticles, the average frequencies of spontaneous activities were significantly decreased compared with control groups (0.65 ± 0.13 Hz, 0.34 ± 0.07 Hz, *p < 0.05). These results indicated that nano-alumina might have adverse effects on the central nervous system in Drosophila.

Acute effects of electro-acupuncture (EA) on hippocampal long term potentiation (LTP) of perforant path-dentate gyrus granule cells synapse related to memory.

Acupuncture, a traditional Chinese therapeutic method, has been widely used in clinical practice to treat diseases such as stroke, Bell's palsy, Alzheimer disease, Parkinson diseases, dysmenorrhea and chronic pain. Mounting lab data had suggested that electro-acupuncture could alleviate dementia and restore long term potentiation of hippocampus in rat. Clinical data also indicated that electro-acupuncture could improve electrical activity of brain in vascular dementia patients. However, its biological basis and acute effects on hippocampal long term potentiation (LTP) remain not well understood. Therefore, we sought to investigate whether acute electro-acupuncture (acupoints: ST36 and SP6; continuous wave, 2 mV, 2Hz; lasted 20 min) could enhance LTP of perforant path-dentate gyrus granule cells in anesthetized rat and explore its underlying mechanisms. We found that electro-acupuncture could significantly increase PS2/PS 1 in pair pulse test (P <0.05, inter-pulse interval: 20ms and 90ms). When compared to control group, electro-acupuncture could significantly enhance LTP to about 234% which was about 143% of that in control group (P <0.05). It suggested that electro-acupuncture could modulate the function of interneurons in hippocampus hence increase LTP.