4.4 Article

Involvement of Spinal Neurotrophin-3 in Electroacupuncture Analgesia and Inhibition of Spinal Glial Activation in Rat Model of Monoarthritis

Journal

JOURNAL OF PAIN
Volume 12, Issue 9, Pages 974-984

Publisher

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.jpain.2011.03.002

Keywords

Monoarthritis; electroacupuncture; neurotrophin-3; glia; proinflammatory cytokines

Funding

  1. National Natural Science Foundation [30970975, 30821002, 30800332, 31000495]
  2. National Key Basic Research Program of China [2006CB504509, 2007CB512502]
  3. Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT) [IRT0522]
  4. Research Fund for the Doctoral Program of Higher Education of China [20100071120046]
  5. Fundamental Research Funds for the Central Universities
  6. Young Scientist Foundation of Fudan University

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Although electroacupuncture (EA) has been proven to effectively relieve pain associated with arthritis, the underlying mechanism of EA analgesia requires further investigation. Here, the involvement of spinal neurotrophin-3 (NT-3) in EA's analgesic effects on complete Freund's adjuvant (CFA)-induced inflammatory pain was examined. The present study demonstrated that: 1) repeated EA stimulation of ipsilateral GB30 and GB34 acupoints remarkably suppressed CFA-induced hyperalgesia; 2) EA treatment markedly enhanced the upregulation of spinal NT-3 mRNA and protein levels following CFA injection; 3) antisense oligodeoxynucleotides (ODN) specifically against NT-3 intrathecally administered during EA treatment for 7 days significantly attenuated the EA analgesia; and 4) the suppressed expression of spinal GFAP (astrocytic marker), OX-42 (microglial marker) as well as proinflammatory cytokines, interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)-alpha by EA treatment was significantly attenuated following NT-3 antisense ODN delivery. These results suggested that endogenous NT-3 may be involved in the analgesic effect of EA on inflammatory pain in rats, mediated through the inhibition of spinal glial activity as well as proinflammatory cytokine production. Perspective: The present study may initiate a discussion on the possible roles of NT-3/glia/cytokines in the therapeutic effects of acupuncture and provide insight on the mechanism underlie the analgesic effects of acupuncture on pain associated with arthritis. (C) 2011 by the American Pain Society

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