Regulation of cutaneous C-fiber heat nociceptors by nerve growth factor in the developing rat

Abstract

1. Previous work has indicated that nerve growth factor (NGF) is an important factor for the development of nociceptive A-delta fibers. Here we asked if the availability of NGF during the first 2 wk of development can influence the phenotypic development of unmyelinated afferent C-fibers. 2. To do this, we treated newborn rats with antibodies to NGF from postnatal day (PND) 2-14, a treatment known not to lead to cell death, or with exogenous NGF (PND 0-14). Untreated litter mates served as controls. When the animals were mature (5-20 wk later), they were anesthetized (urethan, 1.25 g/kg ip) and single-unit recordings were made from sural nerve C-fibers in dorsal root filaments. To obtain an unbiased estimate of the physiological types present, an electrocutaneous search technique was employed to isolate the location of the putative receptive field of the C-fiber being studied within the sural nerve territory. This technique enabled us to acquire a sample of C-fibers that was unbiased by natural search stimuli which are often damaging to skin. 3. We found that the proportion of C-fibers that could be driven by noxious heat and mechanical stimuli (C-mechanoheat fibers, C-MH) was reduced from 28% (11/40 fibers) of the sample in controls to 10% (3/31 fibers) in anti-NGF treated animals. The C-MH fibers appeared to have been replaced by a novel type of pressure receptor with an unusually low mechanical threshold (mean 0.86 +/- 0.58 compared with 13.0 +/- 8.3 g for control mechanonociceptors).(ABSTRACT TRUNCATED AT 250 WORDS)