Woolf C J, Shortland P, Reynolds M, Ridings J, Doubell T, Coggeshall R E
Department of Anatomy and Developmental Biology, University College London, England.
J Comp Neurol. 1995 Sep 11;360(1):121-34. doi: 10.1002/cne.903600109.
We have investigated the time course and extent to which peripheral nerve lesions cause a morphological reorganization of the central terminals of choleragenoid-horseradish peroxidase (B-HRP)-labelled primary afferent fibers in the mammalian dorsal horn. Choleragenoid-horseradish peroxidase is retrogradely transported by myelinated (A) sensory axons to laminae I, III, IV and V of the normal dorsal horn of the spinal cord, leaving lamina II unlabelled. We previously showed that peripheral axotomy results in the sprouting of numerous B-HRP-labelled large myelinated sensory axons into lamina II. We show here that this spread of B-HRP-labelled axons into lamina II is detectable at 1 week, maximal by 2 weeks and persists for over 6 months postlesion. By 9 months, however, B-HRP fibers no longer appear in lamina II. The sprouting into lamina II occurs whether regeneration is allowed (crush) or prevented (section with ligation), and does not reverse at times when peripheral fibers reinnervate the periphery. We also show that 15 times more synaptic terminals in lamina II are labelled by B-HRP 2 weeks after axotomy than in the normal. We interpret this as indicating that the sprouting fibers are making synaptic contacts with postsynaptic targets. This implies that A-fiber terminal reorganization is a prominent and long-lasting but not permanent feature of peripheral axotomy. We also provide evidence that this sprouting is the consequence of a combination of an atrophic loss of central synaptic terminals and the conditioning of the sensory neurons by peripheral axotomy. The sprouting of large sensory fibers into the spinal territory where postsynaptic targets usually receive only small afferent fiber input may bear on the intractable touch-evoked pain that can follow nerve injury.
我们研究了周围神经损伤导致霍乱毒素结合辣根过氧化物酶（B-HRP）标记的初级传入纤维在哺乳动物背角的中枢终末发生形态重组的时间进程和程度。霍乱毒素结合辣根过氧化物酶由有髓鞘（A）感觉轴突逆行运输至脊髓正常背角的Ⅰ、Ⅲ、Ⅳ和Ⅴ层，Ⅱ层无标记。我们先前表明，周围轴突切断导致大量B-HRP标记的有髓鞘大感觉轴突发芽进入Ⅱ层。我们在此表明，B-HRP标记的轴突向Ⅱ层的这种扩展在损伤后1周即可检测到，2周时达到最大，并在损伤后持续6个月以上。然而，到9个月时，B-HRP纤维不再出现在Ⅱ层。无论允许再生（挤压）还是阻止再生（结扎切断），都会发生向Ⅱ层的发芽，并且在外周纤维重新支配外周时不会逆转。我们还表明，轴突切断后2周，Ⅱ层中被B-HRP标记的突触终末比正常情况下多15倍。我们将此解释为表明发芽纤维正在与突触后靶点形成突触联系。这意味着A纤维终末重组是周围轴突切断的一个突出且持久但非永久性的特征。我们还提供证据表明，这种发芽是中枢突触终末萎缩性丧失和周围轴突切断对感觉神经元产生的条件作用共同作用的结果。大感觉纤维向突触后靶点通常仅接受小传入纤维输入的脊髓区域发芽，可能与神经损伤后随之而来的顽固性触摸诱发疼痛有关。
