Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain
Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain
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DOI：
10.1016/0306-4522(95)00343-h
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发表时间：
1996-01-01
期刊：
影响因子：
3.3
通讯作者：
Basbaum, AI
中科院分区：
文献类型：
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作者：
Abbadie, C;Brown, JL;Basbaum, AI
许多研究表明，初级传入源性神经肽P物质通过神经激肽-1/P物质受体在脊髓水平的伤害性信息传递中发挥作用。免疫细胞化学研究表明，P物质受体集中在浅层背角I层的神经元。由于受体的数量和分布的改变可能是持续性疼痛的基础，我们使用免疫细胞化学研究了两种非常不同的大鼠持续性疼痛模型中受体的分布：慢性炎症，这与P物质水平增加有关，坐骨神经节，这与背角P物质水平降低有关。通过单侧后爪注射完全弗氏佐剂产生炎症，我们报告在两种损伤模型中背角浅层P物质受体免疫反应性均上调。在研究的所有时间点（诱导炎症后最多一周和坐骨神经切除后最多两周）均发现增加。P物质受体免疫反应性的增强不仅存在于L4节段背角内侧部，即后爪传入传入的输入区域，而且也存在于背角外侧部，在后爪传入神经的吻侧（L1）和尾侧（S1），上-下-下-上-上-下-上-上-下-受体的调节不能仅仅通过背角中P物质浓度的变化来预测。此外，在这些不同的条件下，P物质受体的非地形上调可能有助于在持续性疼痛条件下的背角伤害性感受器的中枢敏感化。
Numerous studies have implicated the primary afferent derived neuropeptide, substance P, which exerts its effects via the neurokinin-1/substance P receptor, in the transmission of nociceptive messages at the level of the spinal cord. Immunocytochemical studies demonstrate that the substance P receptor is concentrated in neurons of lamina I of the superficial dorsal horn. Since alterations in the number and distribution of the receptor may underlie persistent pain conditions, we have used immunocytochemistry to study the distribution of the receptor in two very different rat models of persistent pain: chronic inflammation, which is associated with increased levels of substance P, and sciatic nerve section, which is associated with decreased levels of substance P in the dorsal horn. Inflammation was produced by unilateral hindpaw injection of complete Freund's adjuvant.We report that there is an up-regulation of substance P receptor immunoreactivity in the superficial laminae of the dorsal horn in both injury models. The increase was found at all time points studied (up to one week after induction of inflammation and up to two weeks after sciatic nerve section). The increase in substance P receptor immunoreactivity was not only present in the medial part of the dorsal horn at segment L4, which is the region of input of the afferents from the hindpaw, but also in the lateral parts of the dorsal horn, and at segments rostral (L1) and caudal (S1) to the afferent input from the hindpaw.These results indicate that the up-regulation of the receptor is not predictable merely by the change in the concentration of substance P in the dorsal horn. Furthermore, the non topographic up-regulation of substance P receptor in these different conditions may contribute to the central sensitization of dorsal horn nociceptors under conditions of persistent pain.