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J Neurophysiol 97: 492-502, 2007. First published October 25, 2006; doi:10.1152/jn.00899.2006
0022-3077/07 $8.00
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Sympathetic Sprouting Near Sensory Neurons After Nerve Injury Occurs Preferentially on Spontaneously Active Cells and Is Reduced by Early Nerve Block

Wenrui Xie, Judith Ann Strong, Huiqing Li and Jun-Ming Zhang

Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio

Submitted 23 August 2006; accepted in final form 20 October 2006

Some chronic pain conditions are maintained or enhanced by sympathetic activity. In animal models of pathological pain, abnormal sprouting of sympathetic fibers around large- and medium-sized sensory neurons is observed in dorsal root ganglia (DRGs). Large- and medium-sized cells are also more likely to be spontaneously active, suggesting that sprouting may be related to neuron activity. We previously showed that sprouting could be reduced by systemic or locally applied lidocaine. In the complete sciatic nerve transection model in rats, spontaneous activity initially originates in the injury site; later, the DRGs become the major source of spontaneous activity. In this study, spontaneous activity reaching the DRG soma was reduced by early nerve blockade (local perfusion of the transected nerve with TTX for the 1st 7 days after injury). This significantly reduced sympathetic sprouting. Conversely, increasing spontaneous activity by local nerve perfusion with K+ channel blockers increased sprouting. The hyperexcitability and spontaneous activity of DRG neurons observed in this model were also significantly reduced by early nerve blockade. These effects of early nerve blockade on sprouting, excitability, and spontaneous activity were all observed 4–5 wk after the end of early nerve blockade, indicating that the early period of spontaneous activity in the injured nerve is critical for establishing the more long-lasting pathologies observed in the DRG. Individual spontaneously active neurons, labeled with fluorescent dye, were five to six times more likely than quiescent cells to be co-localized with sympathetic fibers, suggesting a highly localized correlation of activity and sprouting.


Address for reprint requests and other correspondence: J.-M. Zhang, Dept. of Anesthesiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670531, Cincinnati, OH 45267-0531 (E-mail: Jun-Ming.Zhang{at}uc.edu)







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