Time course and nerve growth factor dependence of inflammation-induced alterations in electrophysiological membrane properties in nociceptive primaryafferent neurons

Novel findings of changes in nociceptive dorsal root ganglion (DRG) neurons during hindlimb inflammation induced by complete Freund's adjuvant (CFA) i njections in the hindpaw and hindleg are reported. These include increased maximum fiber following frequency in nociceptive C- and A delta -fiber unit s by 2.7 and 3 times, respectively, and increased incidence of ongoing (spo ntaneous) activity by 3.3 times (to 54%) and 2.4 times (to 27%), respective ly. These changes and the CFA-induced changes in somatic action potential ( AP) configuration in nociceptive neurons (Djouhri and Lawson, 1999) were in complete 24 hr after CFA. The nerve growth factor (NGF) dependence of the i nflammation-induced changes was examined by injecting a synthetic NGF seque stering protein [tyrosine receptor kinase A Ig2 (trkA Ig2)] with CFA and su bsequently into the CFA injection sites. NGF sequestration prevented some C FA-induced changes in nociceptive neurons including: the increased fiber fo llowing frequency (C and A delta), the increased proportions of units with ongoing activity (C and A delta), the decreased AP duration (C and A delta) , but not the decreased afterhyperpolarization (AHP) durations (C, A delta, and A alpha/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 con sistent with processes involving altered protein expression and/or retrogra de transport of factors. These results (1) implicate NGF in regulating infl ammation-induced decreases in AP duration and in increases in firing rate a nd spontaneous activity but not in decreases in AHP duration and (2) sugges t clinical advantages of reducing NGF in some inflammatory pain states.