Woodbury C Jeffery, Kullmann Florenta A, McIlwrath Sabrina L, Koerber H Richard
Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
J Comp Neurol. 2008 May 20;508(3):500-9. doi: 10.1002/cne.21693.
It is widely thought that, after peripheral injury, some low-threshold mechanoreceptive (LTMR) afferents "sprout" into pain-specific laminae (I-II) of the dorsal horn and are responsible for chronic pain states such as mechanical allodynia. Although recent studies have questioned this hypothesis, they fail to account for a series of compelling results from single-fiber analyses showing extensive projections from large-diameter myelinated afferents into nocireceptive layers after nerve injury. Here we show that, in the thoracic spinal cord of naïve adult mouse, all myelinated nociceptors gave rise to terminal projections throughout the superficial dorsal horn laminae (I-II). Most (70%) of these fibers had large-diameter axons with recurving flame-shaped central arbors that projected throughout the dorsal horn laminae I-V. This morphology was reminiscent of that attributed to sprouted LTMRs described in previous studies. After peripheral nerve axotomy, we found that LTMR afferents with narrow, uninflected somal action potentials did not sprout into superficial laminae of the dorsal horn. Only myelinated noiceptive afferents with broad, inflected somal action potentials were found to give rise to recurving collaterals and project into superficial "pain-specific" laminae after axotomy. We conclude that the previously undocumented central morphology of large, myelinated cutaneous nociceptors may very well account for the morphological findings previously thought to require sprouting of LTMRs.
人们普遍认为，在外周神经损伤后，一些低阈值机械感受器（LTMR）传入纤维会“长入”背角的疼痛特异性板层（I-II），并导致诸如机械性异常性疼痛等慢性疼痛状态。尽管最近的研究对这一假说提出了质疑，但这些研究未能解释单纤维分析得出的一系列令人信服的结果，这些结果表明，在神经损伤后，大直径有髓传入纤维会广泛投射到伤害感受层。在这里，我们表明，在未接触过实验的成年小鼠的胸段脊髓中，所有有髓伤害感受器都会在整个背角浅层板层（I-II）产生终末投射。这些纤维中的大多数（70%）具有大直径轴突，其中心分支呈弯曲的火焰状，投射到整个背角板层I-V。这种形态让人联想到先前研究中描述的长入的LTMR的形态。在外周神经轴突切断后，我们发现，具有狭窄、未弯曲的体细胞动作电位的LTMR传入纤维不会长入背角浅层板层。只有具有宽阔、弯曲的体细胞动作电位的有髓伤害感受传入纤维在轴突切断后会产生弯曲的侧支并投射到浅层“疼痛特异性”板层。我们得出结论，此前未被记录的大型有髓皮肤伤害感受器的中枢形态很可能解释了先前认为需要LTMR长入才能出现的形态学发现。
