title: Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain.
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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ftao1@jhmi.edu
authors.forename: Feng
authors.initials: F
authors.lastname: Tao
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.forename: Haiying
authors.initials: H
authors.lastname: Wu
authors.forename: John
authors.initials: J
authors.lastname: Skinner
authors.forename: Andres
authors.initials: A
authors.lastname: Hurtado
authors.forename: Visar
authors.initials: V
authors.lastname: Belegu
authors.forename: Orion
authors.initials: O
authors.lastname: Furmanski
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.forename: John W
authors.initials: JW
authors.lastname: McDonald
authors.forename: Roger A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D053595:Embryonic Stem Cells / Q000166:cytology; D066246:ErbB Receptors / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D009437:Neuralgia / Q000378:metabolism / Q000628:therapy*; D020890:Neuregulin-1 / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage; D051381:Rats; D066247:Receptor, ErbB-4; D020127:Recovery of Function; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000628:therapy*; D033581:Stem Cell Transplantation
chemical_list: D020890:Neuregulin-1; D034741:RNA, Small Interfering; D066246:ErbB Receptors; C587690:Erbb4 protein, mouse; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4