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The Journal of Neuroscience, November 15, 2001, 21(22):8722-8733
Time Course and Nerve Growth Factor Dependence of
Inflammation-Induced Alterations in Electrophysiological Membrane
Properties in Nociceptive Primary Afferent Neurons
Laiche
Djouhri1,
Dave
Dawbarn2,
Alan
Robertson2,
Richard
Newton1, and
Sally N.
Lawson1
1 Department of Physiology, University of Bristol,
Medical School, University Walk, Bristol BS8 TD, United Kingdom, and
2 University Research Center for Neuroendocrinology,
Bristol Royal Infirmary, Bristol BS2 8HW, United Kingdom
Novel findings of changes in nociceptive dorsal root ganglion (DRG)
neurons during hindlimb inflammation induced by complete Freund's
adjuvant (CFA) injections in the hindpaw and hindleg are reported.
These include increased maximum fiber following frequency in
nociceptive C- and A -fiber units by 2.7 and 3 times, respectively,
and increased incidence of ongoing (spontaneous) activity by 3.3 times
(to 54%) and 2.4 times (to 27%), respectively. These changes and the
CFA-induced changes in somatic action potential (AP) configuration in
nociceptive neurons (Djouhri and Lawson, 1999) were incomplete 24 hr
after CFA. The nerve growth factor (NGF) dependence of the
inflammation-induced changes was examined by injecting a synthetic NGF
sequestering protein [tyrosine receptor kinase A Ig2 (trkA Ig2)] with
CFA and subsequently into the CFA injection sites. NGF sequestration
prevented some CFA-induced changes in nociceptive neurons including:
the increased fiber following frequency (C and A), the increased
proportions of units with ongoing activity (C and A), the decreased
AP duration (C and A), but not the decreased afterhyperpolarization
(AHP) durations (C, A, and A / ) (Djouhri and Lawson, 1999). AP
variables of nociceptive units with spontaneous activity were examined.
The time course of electrophysiological changes in nociceptive units is
consistent with processes involving altered protein expression and/or
retrograde transport of factors. These results (1) implicate NGF in
regulating inflammation-induced decreases in AP duration and in
increases in firing rate and spontaneous activity but not in decreases
in AHP duration and (2) suggest clinical advantages of reducing NGF in
some inflammatory pain states.
Key words:
nociceptive neurons; DRG; hyperalgesia; NGF; firing rate; spontaneous activity
Copyright © 2001 Society for Neuroscience 0270-6474/01/21228722-12$05.00/0
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