A possible role for nerve growth factor in the augmentation of sodium channels in models of chronic pain

Inflammation induces an upregulation of sodium channels in sensory neurons. This most likely occurs as a result of the retrograde transport of cytoche mical mediators released during the inflammatory response. The purpose of t his study was to determine the effect of the subcutaneous administration of one such mediator, nerve growth factor (NGF), on the production of sodium channels in neurons of the rat dorsal root ganglion. For this, hindpaw with drawal from either a thermal or mechanical stimulus was measured in rats at selected intervals for up to 2 weeks following injections of NGF. Sodium c hannel augmentation was then examined in dorsal root ganglia using site-spe cific, anti-sodium channel antibodies. Both thermal and mechanical allodyni a was observed between 3 and 12 h post-injection. The hyperalgesic response returned to baseline by approximately 24 h post-injection. Sodium channel labeling was found to increase dramatically in the small neurons of the ass ociated dorsal root ganglia beginning at 23 h, reached maximum intensity by 1 week, and persisted for up to 3 months post-injection. Pre-blocking NGF with anti-NGF prevented the NGF-induced decrease in paw withdrawal latencie s and significantly reduced the intensity of sodium channel labeling. The r esults indicate that NGF is an important mediator both in the development o f acute hyperalgesia and in the stimulation of sodium channel production in dorsal root ganglia during inflammation. (C) 2000 Elsevier Science B.V. Al l rights reserved.