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

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.

Zingiber officinale Roscoe Rhizomes Attenuate Oxaliplatin-Induced Neuropathic Pain in Mice

“…It has been reported that 5-HT 3 receptors are mostly present in unmyelinated C-fibers of the spinal dorsal horn [ 38 ]. However, according to data obtained from others [ 6 ] and our lab [ 10 ], oxaliplatin-induced neuropathic pain is shown to be mostly mediated by myelinated A-fibers rather than by unmyelinated C-fibers [ 6 , 10 ]. Furthermore, in several studies, cold allodynia is reported to be mediated mostly by unmyelinated fibers [ 39 ].…”

“…Oxaliplatin (Sigma Aldrich, St. Louis, MO, USA) was dissolved in a 5% glucose solution at a concentration of 2 mg/mL, as in our previous study [ 10 ]. Oxaliplatin was administered to mice intraperitoneally in an amount of 6 mg/kg.…”

“…Behavior tests were conducted to assess the degree of allodynia in mice, as in our previous study [ 10 ]. Cold allodynia and mechanical allodynia were measured by using the acetone drop and von Frey filament tests, respectively.…”

“…These paresthesia and dysesthesia can initiate acutely within 48 h after its administration [ 4 ] and are known to peak three days after its administration [ 5 ]. For the past several years, our lab has focused its efforts on understanding the mechanism of action of oxaliplatin-induced neuropathic pain [ 6 , 7 ] and on finding an effective treatment that bears no side effects [ 8 , 9 , 10 ]. However, an optimal drug has yet to be found, and the development of alternative strategies is continuously needed.…”

Bee Venom and Its Sub-Components: Characterization, Pharmacology, and Therapeutics

“…A total of 11 studies were published. Three reviews provided a good overview of the therapeutic effect of bee venom [ 6 , 7 , 8 ], and eight original research articles focused on bee venom, melittin, PLA 2 , and apamin [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”