Prolonged Analgesia by Spinal Cord Stimulation Following a Spinal Injury Associated With Activation of Adult Neural Progenitors

L.T. Sun, S. Fleetwood-Walker, R. Mitchell, E.A. Joosten, C.W. Cheung*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Objectives Responses of spinal progenitors to spinal cord stimulation (SCS) following spinal cord injury (SCI) in rats were assessed to reveal their potential contribution to SCS-induced analgesia. Methods Spinal epidural electrodes were implanted in rats at T12 rostral to a quadrant dorsal horn injury at T13. Further groups additionally received either a microlesion to the dorsolateral funiculus (DLF) or gabapentin (10 mg/kg). SCS was performed at 25 Hz for 10 minutes on day 4 (early SCS) and at 10 Hz for 10 minutes on day 8 (late SCS) after injury. Paw withdrawal threshold (PWT) was measured before injury, 30 minutes before or after SCS, and before cull on day 14, followed by immunostaining assessment. Results Paw withdrawal thresholds in uninjured animals (51.0 +/- 4.0 g) were markedly reduced after SCI (17.3 +/- 2.2 g). This was significantly increased by early SCS (38.5 +/- 5.2 g,P < 0.01) and further enhanced by late SCS (50.9 +/- 1.9 g,P < 0.01) over 6 days. Numbers of neural progenitors expressing nestin, Sox2, and doublecortin (DCX) in the spinal dorsal horn were increased 6 days after SCS by 6-fold, 2-fold, and 2.5-fold, respectively (P < 0.05 to 0.01). The elevated PWT evoked by SCS was abolished by DLF microlesions (48.9 +/- 2.6 g vs. 19.0 +/- 3.9 g,P < 0.01) and the number of nestin-positive cells was reduced to the level without SCS (P < 0.05). Gabapentin enhanced late SCS-induced analgesia from 37.0 +/- 3.9 g to 54.0 +/- 0.8 g (P < 0.01) and increased gamma-aminobutyric acid (GABA)-ergic neuronal marker vesicular GABA transporter-positive newborn cells 2-fold (P < 0.01). Conclusions Spinal progenitor cells appear to be activated by SCS via descending pathways, which may be enhanced by gabapentin and potentially contributes to relief of SCI-induced neuropathic pain.

Original languageEnglish
Pages (from-to)859-877
Number of pages19
JournalPain Practice
Issue number8
Publication statusPublished - 1 Nov 2020


  • chronic pain
  • gabapentin
  • hippocampal
  • mechanisms
  • neural progenitors
  • neurogenesis
  • neuromodulation
  • neuropathic pain
  • proliferation
  • receptors
  • recovery
  • spinal cord injury
  • spinal cord stimulation


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