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The Journal of Neuroscience, October 1, 1999, 19(19):8509-8516
Overexpression of Nerve Growth Factor in Skin Selectively Affects
the Survival and Functional Properties of Nociceptors
C. L.
Stucky1,
M.
Koltzenburg1,
M.
Schneider1,
M. G.
Engle2,
K. M.
Albers3, and
B. M.
Davis2
1 Department of Neurology, University of
Würzburg, D-97080 Würzburg, Germany, and Departments of
2 Anatomy and Neurobiology and 3 Pathology,
University of Kentucky, Lexington, Kentucky 40536
Mice that overexpress nerve growth factor (NGF-OE) in the skin have
double the normal number of cutaneous sensory neurons, have increased
innervation of the skin and spinal cord, and are hyperalgesic. Here, we
have asked whether the increased cutaneous NGF level results in a
selective survival of only certain functional types of neurons and
whether it changes the properties of cutaneous neurons. Using electron
microscopy, we show that the number of both myelinated and unmyelinated
nociceptors increases substantially in NGF-OE mice by a factor of 3.3 and 1.5, respectively. Using extracellular recordings from single
units, we demonstrate that large myelinated (A ) fibers are unchanged
in prevalence and receptive properties. In contrast, among thin
myelinated (A ) fibers, the percentage of nociceptors increased from
a normal 65 to 97%, consistent with a selective survival of
nociceptors during embryogenesis. These afferents showed a twofold
increase in their mechanical responsiveness, but their heat
responsiveness remained normal. Among unmyelinated (C) fibers, there
was a profound increase in the percentage of heat responsive neurons
from a normal 42 to 96%. This change cannot be accounted for by a
selective survival of heat-sensitive neurons. Unmyelinated nociceptors
increased fourfold in their thermal responsiveness but decreased in
mechanical responsiveness. Therefore, target-derived NGF selectively
rescues nociceptors during the period of programmed cell death with
different efficacy for thin myelinated or unmyelinated fibers. NGF also affects the response to noxious heat or mechanical stimuli in each
group differently, implying specific regulations of transduction processes rather than general changes of excitability.
Key words:
neurotrophin; p75; pain; programmed cell death; sensory
neuron; trk
Copyright © 1999 Society for Neuroscience 0270-6474/99/19198509-08$05.00/0
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