Time course and nerve growth factor dependence of inflammation-induced alterations in electrophysiological membrane properties in nociceptive primary afferent neurons.
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 Adelta-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 Adelta), the increased proportions of units with ongoing activity (C and Adelta), the decreased AP duration (C and Adelta), but not the decreased afterhyperpolarization (AHP) durations (C, Adelta, and Aalpha/beta) (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.
Djouhri
L
L
Department of Physiology, University of Bristol, Medical School, University Walk, Bristol BS8 TD, United Kingdom. l.djouhri@bristol.ac.uk
Dawbarn
D
D
Robertson
A
A
Newton
R
R
Lawson
S N
SN
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time
D005620:Freund's Adjuvant; D020932:Nerve Growth Factor