Erythropoietin reduces Schwann cell TNF-α, Wallerian degeneration and pain-related behaviors after peripheral nerve injury

被引：77

作者：

Campana, WM ^{[1
]}

Li, XQ

Shubayev, VI

Angert, M

Cai, K

Myers, RR

机构：

[1] Univ Calif San Diego, Sch Med, Dept Anesthesiol, La Jolla, CA 92093 USA

[2] VA Healthcare Syst, San Diego, CA USA

[3] Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA

来源：

EUROPEAN JOURNAL OF NEUROSCIENCE | 2006年 / 23卷 / 03期

关键词：

glial activation; neuropathic pain; rat; real time PCR; Schwann cell;

D O I：

10.1111/j.1460-9568.2006.04606.x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Chronic sciatic nerve constriction injury (CCI) induces Wallerian degeneration and exaggerated pain-like behaviors. These effects are mediated in large part by pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). In this study, we demonstrate that systemically administered recombinant human erythropoietin (rhEpo) facilitates recovery from chronic neuropathic pain associated with CCI in rats. Because TNF-alpha has been implicated in the development of pain-related behaviors, we measured TNF-alpha mRNA at the nerve injury site. Systemically or locally administered rhEpo decreased TNF-alpha mRNA, compared with that observed in untreated animals. RhEpo also significantly (P < 0.05) decreased axonal degeneration. Immunohistochemistry of CCI nerve showed abundant TNF-alpha in Schwann cells, axoplasm and macrophages. In rhEpo-treated animals, TNF-alpha immunopositivity was decreased selectively in Schwann cells. These results suggest a model in which rhEpo counteracts the effects of TNF-alpha in CCI by blocking expression of TNF-alpha in Schwann cells. To further test this model, we studied primary Schwann cell cultures. RhEpo inhibited TNF-alpha expression in response to lipopolysaccharide, supporting the conclusions of our in vivo CCI experiments. In addition, rhEpo directly counteracted Schwann cell death induced by exogenously added TNF-alpha in vitro. These results indicated that rhEpo regulates TNF-alpha by multiple mechanisms; rhEpo regulates TNF-alpha mRNA expression by Schwann cells but also may directly counteract TNF-alpha signaling pathways that lead to injury, chronic pain and/or death.

引用

页码：617 / 626

页数：10

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