REGULATION OF CUTANEOUS C-FIBER HEAT NOCICEPTORS BY NERVE GROWTH-FACTOR IN THE DEVELOPING RAT
REGULATION OF CUTANEOUS C-FIBER HEAT NOCICEPTORS BY NERVE GROWTH-FACTOR IN THE DEVELOPING RAT
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DOI：
10.1152/jn.1994.71.3.941
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发表时间：
1994-03-01
影响因子：
2.5
通讯作者：
MENDELL, LM
中科院分区：
文献类型：
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作者：
LEWIN, GR;MENDELL, LM
1.已有研究表明，神经生长因子(NGF)是伤害性A-Delta纤维发育的重要因素。在这里，我们问的是，在发育的前2周，NGF的可用性是否会影响无髓传入C纤维的表型发育。为此，我们用出生后2-14天(PND)2-14天的NGF抗体(一种已知不会导致细胞死亡的治疗)或外源性NGF(PND 0-14)治疗新生大鼠。未经处理的窝友作为对照。动物成熟后(5~20wk后)麻醉(乌拉坦，1.25g/kg ip)，以背根细丝中的腓肠神经C纤维为单位进行记录。为了获得对存在的生理类型的无偏见的估计，采用了一种电皮肤搜索技术来分离被研究的C纤维的假定感受场在腓肠神经区域内的位置。这项技术使我们能够获得不受自然搜索刺激的偏向的C纤维样本，而自然搜索刺激通常对皮肤有害。我们发现，能被伤害性热和机械刺激驱动的C纤维(C-机械热纤维，C-MH)的比例从对照组的28%(11/40)减少到抗NGF处理组的10%(3/31)。C-MH纤维似乎已经被一种新型的压力感受器所取代，其机械阈值异常低(平均0.86+/-0.58克，而对照组为13.0+/-8.3克)。相比之下，新生儿NGF治疗使C-MH纤维的采样比例增加到60%(25/42纤维)。新生儿NGF治疗似乎没有导致C纤维对机械刺激的任何敏化。即使通过治疗使动物对机械刺激产生行为过敏性疼痛，情况也是如此。这些结果表明，在生命的前2周，NGF的可获得性可能是决定C纤维对伤害性热的反应性的重要因素。
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 The C-MH fibers appeared to have been replaced by a novel type of pressure receptor with an unusually low mechanical threshold (mean 0.86 +/- 0.58 compared with 13.0 +/- 8.3 g for control mechanonociceptors). In contrast, neonatal NGF treatment increased the proportion of C-MH fibers sampled to 60% (25/42 fibers).4. The neonatal NGF treatments did not appear to lead to any sensitization of C-fibers to mechanical stimuli. This was true even when the animals were rendered behaviorally hyperalgesic to mechanical stimuli by the treatment.5. These results suggest that the availability of NGF during the first 2 wk of life may be important in determining the responsiveness of C-fibers to noxious heat.