Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model

Chia En Wong, Chia Ying Hu, Po Hsuan Lee, Chi Chen Huang, Han Wei Huang, Chih Yuan Huang, Hsin Tien Lo, Wentai Liu, Jung Shun Lee

研究成果: Article同行評審

9 引文 斯高帕斯(Scopus)


Background: Neuropathic pain (NP) is characterized by abnormal activation of pain conducting pathways and manifests as mechanical allodynia and thermal hypersensitivity. Peripheral nerve stimulation is used for treatment of medically refractory chronic NP and has been shown to reduce neuroinflammation. However, whether sciatic nerve stimulation (SNS) is of therapeutic benefit to NP remains unclear. Moreover, the optimal frequency for SNS is unknown. To address this research gap, we investigated the effect of SNS in an acute NP rodent model. Methods: Rats with right L5 nerve root ligation (NRL) or Sham surgery were used. Ipsilateral SNS was performed at 2 Hz, 20 Hz, and 60 Hz frequencies. Behavioral tests were performed to assess pain and thermal hypersensitivity before and after NRL and SNS. Expression of inflammatory proteins in the L5 spinal cord and the immunohistochemical alterations of spinal cord astrocytes and microglia were examined on post-injury day 7 (PID7) following NRL and SNS. The involvement of the descending pain modulatory pathway was also investigated. Results: Following NRL, the rats showed a decreased pain threshold and latency on the von Frey and Hargreaves tests. The immunofluorescence results indicated hyperactivation of superficial spinal cord dorsal horn (SCDH) neurons. Both 2-Hz and 20-Hz SNS alleviated pain behavior and hyperactivation of SCDH neurons. On PID7, NRL resulted in elevated expression of spinal cord inflammatory proteins including NF-κB, TNF-α, IL-1β, and IL-6, which was mitigated by 2-Hz and 20-Hz SNS. Furthermore, 2-Hz and 20-Hz SNS suppressed the activation of spinal cord astrocytes and microglia following NRL on PID7. Activity of the descending serotoninergic pain modulation pathway showed an increase early on PID1 following 2-Hz and 20-Hz SNS. Conclusions: Our results support that both 2-Hz and 20-Hz SNS can alleviate NP behaviors and hyperactivation of pain conducting pathways. We showed that SNS regulates neuroinflammation and reduces inflammatory protein expression, astrocytic gliosis, and microglia activation. During the early post-injury period, SNS also facilitates the descending pain modulatory pathway. Taken together, these findings support the therapeutic potential of SNS for acute NP.

期刊Journal of Neuroinflammation
出版狀態Published - 2022 12月

All Science Journal Classification (ASJC) codes

  • 一般神經科學
  • 免疫學
  • 神經內科
  • 細胞與分子神經科學


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