Peripheral nerve injury is associated with spinal microgliosis which plays a pivotal role in the development of neuropathic pain behavior. Several agents of primary afferent origin causing the microglial reaction have been identified, but the type(s) of primary afferents that release these mediators are still unclear. In this study, specific labeling of C-fiber spinal afferents by lectin histochemistry and selective chemodenervation by capsaicin were applied to identify the type(s) of primary afferents involved in the microglial response. Comparative quantitative morphometric evaluation of the microglial reaction in central projection territories of intact and injured peripheral nerves in the superficial (laminae I and II) and deep (laminae III and IV) spinal dorsal horn revealed a significant, about three-fold increase in microglial density after transection of the sciatic or the saphenous nerve. Prior perineural treatment of these nerves with capsaicin, resulting in a selective defunctionalization of C-fiber afferent fibers failed to affect spinal microgliosis. Similarly, peripheral nerve injury-induced increase in microglial density was unaffected in rats treated neonatally with capsaicin known to result in a near-total loss of C-fiber dorsal root fibers. Perineural treatment with capsaicin per se did not evoke a significant increase in microglial density. These observations indicate that injury-induced spinal microgliosis may be attributed to phenotypic changes in injured myelinated primary afferent neurons, whereas the contribution of C-fiber primary sensory neurons to this neuroimmune response is negligible. Spinal myelinated primary afferents may play a hitherto unrecognized role in regulation of neuroimmune and perisynaptic microenvironments of the spinal dorsal horn.

中文翻译：

---

先前使用辣椒素进行神经周围或新生儿治疗不会改变周围神经损伤引起的脊髓小胶质细胞增生的发展


周围神经损伤与脊髓小胶质细胞增生相关，脊髓小胶质细胞增生在神经性疼痛行为的发展中起着关键作用。引起小胶质细胞反应的几种初级传入源因子已被鉴定，但释放这些介质的初级传入源的类型仍不清楚。在本研究中，通过凝集素组织化学对 C 纤维脊髓传入神经进行特异性标记，并通过辣椒素进行选择性化学去神经，以鉴定参与小胶质细胞反应的初级传入神经的类型。对脊髓背角浅层（I 和 II 层）和深层（III 和 IV 层）完整和受损周围神经中央投射区域的小胶质细胞反应进行比较定量形态测量，结果显示小胶质细胞密度显着增加，约三倍坐骨神经或隐神经横断后。之前用辣椒素对这些神经进行神经周围治疗，导致 C 纤维传入纤维选择性去功能，但未能影响脊髓小胶质细胞增生。同样，在用辣椒素治疗的新生大鼠中，周围神经损伤引起的小胶质细胞密度增加未受影响，已知辣椒素会导致 C 纤维背根纤维几乎完全丧失。用辣椒素本身进行神经周围治疗并没有引起小胶质细胞密度的显着增加。这些观察结果表明，损伤引起的脊髓小胶质细胞增生可能归因于受损的有髓鞘初级传入神经元的表型变化，而 C 纤维初级感觉神经元对这种神经免疫反应的贡献可以忽略不计。 脊髓有髓鞘初级传入神经可能在调节脊髓背角的神经免疫和突触周围微环境中发挥迄今为止未被认识的作用。