Journal of Pain Research (Dec 2020)

Vagus Nerve Stimulation Transiently Mitigates Chemotherapy-Induced Peripheral Neuropathy in Rats

  • Zhang R,
  • Gan Y,
  • Li J,
  • Feng Y

Journal volume & issue
Vol. Volume 13
pp. 3457 – 3465

Abstract

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Ran Zhang,1 Yu Gan,1 Jun Li,2 Yi Feng1,2 1Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Pain Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jun Li; Yi Feng No. 11 Xi Zhi Men Nan Da Jie, Xicheng District, Beijing, People’s Republic of ChinaTel +86-1088325581Email [email protected]: Chemotherapy-induced peripheral neuropathy is a severe side effect of chemotherapeutic agents. Vagus nerve stimulation attenuates neuroinflammation by activating the cholinergic anti-inflammatory pathway and thus may attenuate CIPN.Methods: Adult male Sprague-Dawley rats received intraperitoneal paclitaxel injection (2 mg/kg) every other day for a total of 4 injections. Three weeks later, the left cervical vagus nerve was exposed under general anesthesia, and the rats randomly received 20-min stimulation (1 V, 2 ms, 5 Hz, 30 s ON/5 min OFF) or sham stimulation. Heat and mechanical pain sensitivity was evaluated using Hargreaves and von Frey tests before and after treatment (n=12 per group per time point). Additionally, rats receiving paclitaxel or saline but no surgery were included. Expression of representative pro- and anti-inflammatory cytokines in dorsal root ganglia was assessed by Western blotting assays and immunohistochemistry.Results: Paclitaxel significantly reduced the sensitivity for heat (withdrawal latency: paclitaxel 6.16 ± 0.54 s vs saline 9.93 ± 0.78 s, p< 0.001) and mechanical pain (withdrawal frequency: paclitaxel 32.22 ± 15.51% vs saline 3.33 ± 4.92%, p< 0.001). Compared with sham-stimulated rats, rats receiving vagus nerve stimulation had significantly higher sensitivity for heat (withdrawal latency: VNS 10.28 ± 1.15 s vs sham 6.27 ± 0.56 s, p< 0.001) and mechanical pain (withdrawal frequency: VNS 10.00 ± 9.54% vs Sham 31.67 ± 18.99%, p=0.003) on +1 day, but not 7 days later (withdrawal latency: VNS 6.97 ± 1.13 s vs Sham 6.23 ± 0.79 s, p=0.080; withdrawal frequency: VNS 21.67 ± 11.93% vs Sham 23.33 ± 7.79%, p=0.689). Western blotting assays and immunohistochemistry revealed that interleukin-10 level was elevated in the dorsal root ganglia of rats receiving vagus nerve stimulation while no apparent changes in NF-κB or TNF-α levels were observed.Conclusion: Vagus nerve stimulation could transiently attenuate paclitaxel-induced hyperalgesia in rats. Future studies are needed to investigate whether stimulation with different protocols could achieve durable effects.Keywords: chemotherapy-induced peripheral neuropathy, neuroinflammation, vagus nerve stimulation, cholinergic anti-inflammatory pathway, interleukin-10

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