de Castro F, Silos-Santiago I, López de Armentia M, Barbacid M, Belmonte C
Instituto de Neurociencias, Universidad Miguel Hernandez, San Juan de Alicante, Spain.
Eur J Neurosci. 1998 Jan;10(1):146-52. doi: 10.1046/j.1460-9568.1998.00037.x.
Most primary sensory neurones depend on neurotrophins for survival. Mutant mice in which TrkA, the high-affinity receptor for nerve growth factor (NGF), has been inactivated lack nociceptive neurones in sensory ganglia and do not respond to noxious stimuli. The cornea of the eye is innervated by trigeminal neurones that are activated by noxious mechanical, thermal and chemical stimuli. In the human cornea, these stimuli evoke only sensations of pain. We have analysed the innervation pattern and the response to noxious stimulation of the cornea of trkA (-/-) mutant mice. Corneal nerves were stained with the gold chloride impregnation method. Corneal sensitivity to noxious stimuli was assessed by counting blinking movements evoked by von Frey hairs, topical application of saline at different temperatures and application of acetic acid and capsaicin at different concentrations. In the cornea of trkA (-/-) mutant animals, we observed a drastic reduction in the number of nerve trunks and branches in the corneal stroma. Furthermore, quantitative analysis of the number of thin nerve terminals revealed a marked decrease in the corneal epithelium of trkA (-/-) mice when compared to those present in wild type and trkA (+/-) animals. The blinking response of trkA (-/-) mice to mechanical, thermal and chemical noxious stimuli was also significantly reduced. These results indicate that the population of corneal sensory neurones is markedly depleted in trkA (-/-) mutant mice. However, a small portion of corneal sensory neurones survive in these mice suggesting that they may be NGF independent. On the basis of our results, we propose that these surviving cells are polymodal nociceptive neurones, sensitive to mechanical stimulation, noxious heat and acid.
大多数初级感觉神经元依赖神经营养因子来维持生存。在其中神经生长因子（NGF）的高亲和力受体TrkA已失活的突变小鼠中，感觉神经节中缺乏伤害性神经元，并且对有害刺激无反应。眼睛的角膜由三叉神经元支配，这些神经元可被有害的机械、热和化学刺激激活。在人类角膜中，这些刺激仅引起疼痛感。我们分析了trkA（-/-）突变小鼠角膜的神经支配模式以及对有害刺激的反应。用氯化金浸染法对角膜神经进行染色。通过计数由von Frey毛发诱发的眨眼动作、在不同温度下局部应用盐水以及应用不同浓度的乙酸和辣椒素来评估角膜对有害刺激的敏感性。在trkA（-/-）突变动物的角膜中，我们观察到角膜基质中神经干和分支的数量急剧减少。此外，与野生型和trkA（+/-）动物相比，对细神经末梢数量的定量分析显示trkA（-/-）小鼠角膜上皮中的数量明显减少。trkA（-/-）小鼠对机械、热和化学有害刺激的眨眼反应也显著降低。这些结果表明，trkA（-/-）突变小鼠角膜感觉神经元的数量明显减少。然而，这些小鼠中仍有一小部分角膜感觉神经元存活，这表明它们可能不依赖NGF。根据我们的结果，我们推测这些存活的细胞是多模式伤害性神经元，对机械刺激、有害热和酸敏感。
