The Journal of Neuroscience, September 1, 2002, 22(17):7746-7753
Degeneration of Myelinated Efferent Fibers Induces Spontaneous
Activity in Uninjured C-Fiber Afferents
Gang
Wu1,
Matthias
Ringkamp1,
Beth B.
Murinson2,
Esther M.
Pogatzki1,
Timothy V.
Hartke1,
Himali M.
Weerahandi1,
James N.
Campbell1, 4,
John W.
Griffin2, 3, and
Richard A.
Meyer1, 4
Departments of 1 Neurosurgery, 2 Neurology,
and 3 Neuroscience, and the 4 Applied Physics
Laboratory, Johns Hopkins University, Baltimore, Maryland 21287
We demonstrated recently that uninjured C-fiber nociceptors in the
L4 spinal nerve develop spontaneous activity after transection of the
L5 spinal nerve. We postulated that Wallerian degeneration leads to an
alteration in the properties of the neighboring, uninjured afferents
from adjacent spinal nerves. To explore the role of degeneration of
myelinated versus unmyelinated fibers, we investigated the effects of
an L5 ventral rhizotomy in rat. This lesion leads to degeneration
predominantly in myelinated fibers. Mechanical paw-withdrawal
thresholds were assessed with von Frey hairs, and teased-fiber
techniques were used to record from single C-fiber afferents in the L4
spinal nerve. Behavioral and electrophysiological data were collected
in a blinded manner. Seven days after surgery, a marked decrease in
withdrawal thresholds was observed after the ventral rhizotomy but not
after the sham operation. Single fiber recordings revealed
low-frequency spontaneous activity in 25% of the C-fiber afferents
8-10 d after the lesion compared with only 11% after sham operation.
Paw-withdrawal thresholds were inversely correlated with the incidence
of spontaneous activity in high-threshold C-fiber
afferents. In normal animals, low-frequency electrocutaneous
stimulation at C-fiber, but not A-fiber, strength produced behavioral
signs of secondary mechanical hyperalgesia on the paw. These results
suggest that degeneration in myelinated efferent fibers is
sufficient to induce spontaneous activity in C-fiber afferents and
behavioral signs of mechanical hyperalgesia. Ectopic spontaneous
activity from injured afferents was not required for the development of
the neuropathic pain behavior. These results provide additional
evidence for a role of Wallerian degeneration in neuropathic pain.
Key words:
neuropathic pain; nerve injury; sensitization; hyperalgesia; neuropathy; Wallerian degeneration; unmyelinated
cutaneous afferent; in vivo; single nerve fiber
recording
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177746-08$05.00/0
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