Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain

Feng Tao, Qun Li, Su Liu, Haiying Wu, John Skinner, Andres Hurtado, Visar Belegu, Orion Furmanski, Ya Yang, John W. McDonald, Roger A Johns

Research output: Contribution to journalArticle

Abstract

Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination in the injured spinal cord and reduces SCI-induced chronic neuropathic pain. Moreover, we found that SCI reduces the protein level of neuregulin-1 and ErbB4 in the injured spinal cord and that OPC transplantation enhances the spinal expression of both proteins after SCI. Finally, intrathecal injection of neuregulin-1 small interfering RNA, but not the control nontarget RNA, diminishes OPC transplantation-produced remyelination and reverses the antinociceptive effect of OPC transplantation. Our findings suggest that the transplantation of embryonic stem cell-derived OPCs is an appropriate therapeutic intervention for treatment of SCI-induced chronic neuropathic pain, and that neuregulin-1/ErbB signaling plays an important role in central remyelination under pathological conditions and contributes to the alleviation of such pain.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalStem Cells
Volume31
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Neuregulin-1
Neuralgia
Cell- and Tissue-Based Therapy
Spinal Cord Injuries
Chronic Pain
Oligodendroglia
Stem Cells
Cell Transplantation
Spinal Cord
Transplantation
Pain
Spinal Injections
Contusions
Embryonic Stem Cells
Small Interfering RNA
Proteins
Therapeutics
Observation
RNA
Wounds and Injuries

Keywords

  • Chronic neuropathic pain
  • Neuregulin-1/ErbB signaling
  • Spinal cord injury
  • Stem cell transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain. / Tao, Feng; Li, Qun; Liu, Su; Wu, Haiying; Skinner, John; Hurtado, Andres; Belegu, Visar; Furmanski, Orion; Yang, Ya; McDonald, John W.; Johns, Roger A.

In: Stem Cells, Vol. 31, No. 1, 01.2013, p. 83-91.

Research output: Contribution to journalArticle

Tao, F, Li, Q, Liu, S, Wu, H, Skinner, J, Hurtado, A, Belegu, V, Furmanski, O, Yang, Y, McDonald, JW & Johns, RA 2013, 'Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain', Stem Cells, vol. 31, no. 1, pp. 83-91. https://doi.org/10.1002/stem.1258
Tao, Feng ; Li, Qun ; Liu, Su ; Wu, Haiying ; Skinner, John ; Hurtado, Andres ; Belegu, Visar ; Furmanski, Orion ; Yang, Ya ; McDonald, John W. ; Johns, Roger A. / Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain. In: Stem Cells. 2013 ; Vol. 31, No. 1. pp. 83-91.
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