Kar S, Gibson S J, Scaravilli F, Jacobs J M, Aber V R, Polak J M
Department of Histochemistry, Royal Postgraduate Medical School, London, United Kingdom.
Cell Tissue Res. 1989 Feb;255(2):451-66. doi: 10.1007/BF00224131.
The mutilated foot rat is a mutant with autosomal recessive sensory neuropathy and frequent mutilation of the hindlimbs. Decreased numbers of dorsal root ganglion cells and diminished sensitivity to painful stimuli are characteristics of these animals. By use of immunocytochemistry, changes in the distributions of peptides involved in sensory and/or autonomic regulation, i.e., calcitonin gene-related peptide (CGRP), tachykinins, enkephalin and neuropeptide Y in spinal cord, dorsal root ganglia and skin of these animals, were studied. In comparison with normal litter-mate controls, the dorsal horn of mutilated foot rats contained substantially fewer CGRP- and tachykinin-immunoreactive fibres but more fibres immunoreactive for enkephalin. Many enkephalin-immunoreactive cell bodies were also found in the dorsal horn of the mutants, by contrast none were visible in control animals. Neuropeptide Y immunoreactivity was, however, unchanged in the spinal cord of the mutants. In the dorsal root ganglia of the mutants, the number of CGRP- or tachykinin-immunoreactive cells and their proportion to total neuronal numbers were significantly less in comparison with normal controls. The diameter range of CGRP- and tachykinin-immunoreactive cells shifted from small (15-25 microns) to medium size (25-45 microns) as revealed by frequency distribution histograms. The skin from the affected fore- and hindlimbs of the mutant rats, in keeping with fewer CGRP- and tachykinin-immunoreactive cells in the dorsal root ganglia, contained substantially less fibres immunoreactive for CGRP and tachykinins; a difference that was not seen in skin of unaffected areas (whiskers and snout). By contrast, neuropeptide Y-immunoreactive fibres showed a normal distribution around blood vessels and sweat glands of mutilated foot rats. The data suggest that diminished pain perception in the mutilated foot rat is related to loss of peptide-containing sensory neurones. Furthermore, the intraspinal increase of enkephalinergic neurons in the dorsal horn, concomitant with the decreased number of primary sensory neurones, may also play a contributory rôle in reducing pain thresholds.
残足大鼠是一种具有常染色体隐性感觉神经病且后肢频繁自残的突变体。背根神经节细胞数量减少以及对疼痛刺激的敏感性降低是这些动物的特征。通过免疫细胞化学方法，研究了这些动物脊髓、背根神经节和皮肤中参与感觉和/或自主调节的肽类，即降钙素基因相关肽（CGRP）、速激肽、脑啡肽和神经肽Y分布的变化。与正常同窝对照相比，残足大鼠的背角中CGRP和速激肽免疫反应性纤维明显减少，但脑啡肽免疫反应性纤维较多。在突变体的背角中还发现了许多脑啡肽免疫反应性细胞体，相比之下，对照动物中未见此类细胞体。然而，突变体脊髓中的神经肽Y免疫反应性没有变化。与正常对照相比，突变体背根神经节中CGRP或速激肽免疫反应性细胞的数量及其占总神经元数量的比例明显减少。频率分布直方图显示，CGRP和速激肽免疫反应性细胞的直径范围从小（15 - 25微米）转变为中等大小（25 - 45微米）。与背根神经节中CGRP和速激肽免疫反应性细胞较少一致，突变大鼠受影响的前肢和后肢皮肤中CGRP和速激肽免疫反应性纤维也明显较少；未受影响区域（胡须和口鼻部）的皮肤中未见这种差异。相比之下，神经肽Y免疫反应性纤维在残足大鼠的血管和汗腺周围分布正常。数据表明，残足大鼠疼痛感知减弱与含肽感觉神经元的丧失有关。此外，背角中脑啡肽能神经元的脊髓内增加，与初级感觉神经元数量减少同时出现，也可能在降低痛阈中起作用。
