BACKGROUND Acupuncture has been used to treat a wide variety of diseases, disorders, and conditions for more than 2,500 years. While the anatomical structures of acupuncture points (or acupoints) are largely unknown, our previous studies have suggested that many acupoints can be identified as cutaneous neurogenic inflammatory spots (neurogenic spots or Neuro-Sps), arising from the release of neuropeptides from activated small diameter sensory afferents at topographically distinct body surfaces due to the convergence of visceral and somatic afferents. In turn, the neuropeptides released during neurogenic inflammation may play important roles in the effects of acupuncture as well as the formation of acupoints. Thus, the present study has focused on the role of substance P (SP) in acupuncture signal transduction and effects. METHODS Neuro-Sps were detected by using in vivo fluorescence imaging after intravenous injection of Evans blue dye (EBD) and compared with traditional acupoints. Stimulatory effects of the Neuro-Sps were examined in a rat model of immobilization-induced hypertension (IMH). The roles of increased SP in Neuro-Sps were also investigated by using immunohistochemistry, in vivo single-fiber peripheral nerve recordings, and in vivo midbrain extracellular recordings. RESULTS Neurogenic inflammation quickly appeared at acupoints on the wrist and was fully developed within 15 min in IMH model. The Neuro-Sps showed an increased release of SP from afferent nerve terminals. Mechanical stimulation of these Neuro-Sps increased cell excitability in the midbrain (rostral ventrolateral medulla) and alleviated the development of hypertension, which was blocked by the local injection of the SP receptor antagonist CP-99994 into Neuro-Sps prior to acupuncture and mimicked by the local injection of capsaicin. Single fiber recordings of peripheral nerves showed that increased SP into the Neuro-Sps elevated the sensitivity of A- and C-fibers in response to acupuncture stimulation. In addition, the discharge rates of spinal wide dynamic response (WDR) neurons significantly increased following SP or acupuncture treatment in Neuro-Sps in normal rats, but decreased following the injection of CP-99994 into Neuro-Sps in IMH rats. CONCLUSIONS Our findings suggest that SP released during neurogenic inflammation enhances the responses of sensory afferents to the needling of acupoints and triggers acupuncture signaling to generate acupuncture effects.

中文翻译：

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P物质在针灸信号传导中的作用及作用


背景技术针灸用于治疗多种疾病、病症和病症已有 2,500 多年的历史。虽然针灸穴位（或穴位）的解剖结构在很大程度上未知，但我们之前的研究表明，许多穴位可以被识别为皮肤神经源性炎症斑（神经源性斑点或Neuro-Sps），这是由激活的小直径释放神经肽引起的由于内脏和躯体传入的融合，在地形不同的身体表面产生感觉传入。反过来，神经源性炎症过程中释放的神经肽可能在针灸效果以及穴位形成中发挥重要作用。因此，本研究重点关注P物质（SP）在针灸信号转导和效应中的作用。方法静脉注射伊文思蓝染料（EBD）后，采用体内荧光成像技术检测Neuro-Sps，并与传统穴位进行比较。在固定诱发高血压 (IMH) 的大鼠模型中检查了 Neuro-Sps 的刺激作用。还通过使用免疫组织化学、体内单纤维周围神经记录和体内中脑细胞外记录来研究增加的 SP 在 Neuro-Sps 中的作用。结果 IMH模型中神经源性炎症在腕部穴位迅速出现，并在15 min内完全发展。 Neuro-Sps 显示传入神经末梢 SP 释放增加。 对这些 Neuro-Sps 的机械刺激增加了中脑（延髓头侧腹外侧）的细胞兴奋性，并减轻了高血压的发展，针灸前将 SP 受体拮抗剂 CP-99994 局部注射到 Neuro-Sps 中可以阻断高血压的发展，并通过模拟局部注射辣椒素。周围神经的单纤维记录表明，增加进入 Neuro-Sps 的 SP 会提高 A 纤维和 C 纤维对针刺刺激的敏感性。此外，在正常大鼠的 Neuro-Sps 中进行 SP 或针灸治疗后，脊髓宽动态响应 (WDR) 神经元的放电率显着增加，但在 IMH 大鼠的 Neuro-Sps 中注射 CP-99994 后，放电率下降。结论我们的研究结果表明，神经源性炎症过程中释放的SP增强了感觉传入对穴位针刺的反应，并触发针灸信号传导以产生针灸效应。