Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
Research Service, G.V. (Sonny) Montgomery VA Medical Center, Jackson, MS, 39216, USA.
Sci Rep. 2019 Mar 12;9(1):4273. doi: 10.1038/s41598-019-40967-y.
Central sprouting of nociceptive afferents in response to neural injury enhances excitability of nociceptive pathways in the central nervous system, often causing pain. A reliable quantification of central projections of afferent subtypes and their synaptic terminations is essential for understanding neural plasticity in any pathological condition. We previously characterized central projections of cutaneous nociceptive A and C fibers, selectively labeled with cholera toxin subunit B (CTB) and Isolectin B4 (IB4) respectively, and found that they expressed a general synaptic molecule, synaptophysin, largely depending on afferent subtypes (A vs. C fibers) across thoracic dorsal horns. The current studies extended the central termination profiles of nociceptive afferents with synaptoporin, an isoform of synaptophysin, known to be preferentially expressed in C fibers in lumbar dorsal root ganglions. Our findings demonstrated that synaptophysin was predominantly expressed in both peptidergic and IB4-binding C fiber populations in superficial laminae of the thoracic dorsal horn. Cutaneous IB4-labeled C fibers showed comparable expression levels of both isoforms, while cutaneous CTB-labeled A fibers exclusively expressed synaptophysin. These data suggest that central expression of synaptophysin consistently represents synaptic terminations of projecting afferents, at least in part, including nociceptive A-delta and C fibers in the dorsal horn.
伤害性传入纤维在中枢的发芽会增强中枢神经系统中伤害性通路的兴奋性,这通常会导致疼痛。对于理解任何病理条件下的神经可塑性,对传入型纤维亚型的中枢投射及其突触末梢进行可靠的定量分析是至关重要的。我们之前已经对分别用霍乱毒素亚单位 B(CTB)和 I 型别豆素 B4(IB4)选择性标记的皮肤伤害性 A 和 C 纤维的中枢投射进行了描述,并发现它们在胸段背角中大量表达了一种一般的突触分子,即突触素,而这种表达主要依赖于传入型纤维(A 纤维与 C 纤维)的种类。目前的研究扩展了伤害性传入纤维的中枢末端分布图谱,这些纤维用突触小泡蛋白(synaptoporin)进行了标记,突触小泡蛋白是一种突触素同工型,已知在腰椎背根神经节中的 C 纤维中优先表达。我们的研究结果表明,突触素主要在胸段背角浅层的肽能和 IB4 结合的 C 纤维群体中表达。皮肤 IB4 标记的 C 纤维表现出两种同工型相当的表达水平,而皮肤 CTB 标记的 A 纤维则只表达突触素。这些数据表明,突触素在中枢的表达至少在一定程度上一致地代表了投射传入纤维的突触末梢,包括背角中的伤害性 Aδ 和 C 纤维。