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Neurotrophin-3 and Tyrosine Kinase C Have Modulatory Effects on Neuropathic Pain in the Rat Dorsal Root Ganglia

Tender, Gabriel C MD*; Kaye, Alan David MD‡; Li, Yuan-Yuan BS*; Cui, Jian-Guo MD, PhD*

doi: 10.1227/NEU.0b013e318208f9c4

BACKGROUND: Neurotrophin-3 (NT3) and its cognate receptor, tyrosine kinase C (TrkC), have recently been shown to modulate neuropathic pain. Another receptor, the transient receptor potential vanilloid 1, is considered a molecular integrator for nociception. Transient receptor potential vanilloid 1–positive cells can be selectively ablated by Resiniferatoxin (RTX). NT3 changes in the dorsal root ganglia (DRG) after RTX treatment may further define their role in pain modulation.

OBJECTIVE: To demonstrate the role of NT3 and TrkC in intraganglial RTX-induced pain suppression and in neuropathic pain development.

METHODS: Fifty-three rats underwent a photochemical left sciatic nerve injury. Neuropathic animals were treated by RTX injection in the ipsilateral L3-6 DRG. NT3 and TrkC presence in the DRG was evaluated before and after the nerve injury, as well as after RTX treatment.

RESULTS: The RTX injection resulted in pain inhibition. NT3 normally expressed mainly in large- and medium-size neurons. NT3 presence was increased mainly in the small DRG cells of neuropathic animals, and the medium- and large-size neurons of nonallodynic rats. RTX treatment of allodynic rats changed the NT3 distribution to a nonallodynic pattern. TrkC expressed mainly in large/medium-size neurons. After nerve injury, TrkC expression was also increased in the small DRG cells of allodynic animals (although less than NT3), and the medium- and large-size cells of nonallodynic ones. After RTX, TrkC expression gradually decreased, but with persistence in the large DRG cells.

CONCLUSION: NT3 may have antinociceptive effects in the DRG. These effects may be mediated, at least in part, by TrkC in the medium- and large-size DRG neurons.

*Department of Neurosurgery, Neuroscience Center of Excellence, ‡Department of Anesthesiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Received, April 6, 2010.

Accepted, June 7, 2010.

Correspondence: Jian-Guo Cui, MD, PhD, Neuroscience Center, Health Sciences Center, Louisiana State University, 2020 Gravier Street, New Orleans, LA 70112. E-mail:

Copyright © by the Congress of Neurological Surgeons