Bee Venom Acupuncture Attenuates Oxaliplatin-Induced Neuropathic Pain by Modulating Action Potential Threshold in A-Fiber Dorsal Root Ganglia Neurons.

Ji Hwan Lee,Eunhee Yang,Young-Ho Jin,Juan Gang,Woojin Kim

doi:10.3390/toxins12120737

Abstract

Oxaliplatin is a third-generation platinum-based chemotherapeutic drug widely used in colorectal cancer treatment. Although potent against this tumor, it can induce cold and mechanical allodynia even after a single injection. The currently used drugs to attenuate this allodynia can also cause unwanted effects, which limit their use. Bee venom acupuncture (BVA) is widely used in Korean medicine to treat pain. Although the effect of BVA on oxaliplatin-induced neuropathic pain has been addressed in many studies, its action on dorsal root ganglia (DRG) neurons has never been investigated. A single oxaliplatin injection (6 mg/kg, intraperitoneally) induced cold and mechanical allodynia, and BVA (0.1 and 1 mg/kg, subcutaneous, ST36) dose-dependently decreased allodynia in rats. On acutely dissociated lumbar 4–6 DRG neurons, 10 min application of oxaliplatin (100 μM) shifted the voltage-dependence of sodium conductance toward negative membrane potentials in A- but not C-fibers. The resting membrane potential remained unchanged, but the action potential threshold decreased significantly compared to that of the control (p < 0.05). However, 0.1 μg/mL of BVA administration increased the lowered action potential threshold. In conclusion, these results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber DRG neurons.

Highlights

Oxaliplatin is a chemotherapeutic drug widely used in the treatment of advanced metastatic colorectal cancer [1], which is the second highest cause of death due to cancer after lung carcinoma [2].Despite its effect on tumor size reduction, its use can be limited due to peripheral neuropathy rapidly occurring after infusion in up to 80–90% of treated patients
bee venom acupuncture (BVA) administration increased the lowered action potential threshold. These results suggest that BVA may attenuate oxaliplatin-induced neuropathic pain by altering the action potential threshold in A-fiber dorsal root ganglia (DRG) neurons
Four days after oxaliplatin injection, both cold (p and mechanical and mechanical (p < 0.01) allodynia were significantly induced compared to the control group (post(pinjection)

Summary

Introduction

Despite its effect on tumor size reduction, its use can be limited due to peripheral neuropathy rapidly occurring after infusion in up to 80–90% of treated patients. This peripheral neuropathy is characterized by a glove-and-stocking distribution sensory loss, paresthesia, and dysesthesia, which can Toxins 2020, 12, 737; doi:10.3390/toxins12120737 www.mdpi.com/journal/toxins. To prevent or attenuate this oxaliplatin-induced neuropathic pain, various strategies and drugs have been proposed such as “stop and go” strategy, Ca/Mg infusion, glutathione, and duloxetine. The American Society of Clinical Organization guidelines [4] and the Journal of the American Medical Association [5] recommended duloxetine, which is a well-established anticonvulsant and analgesic drug, to mitigate oxaliplatin-induced pain.

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