最近一项发表在美国国家科学院院刊（Proceedings of the National Academy of Sciences）上的研究阐明了痛觉神经递质P物质（SP）在痛觉感受及传导中的作用，为痛觉的研究及治疗提供了新的思路。
SP是一种痛觉神经递质，在很多器官中传导痛觉。虽然肌肉组织和脑脊液中的SP水平过高通常与慢性肌肉痛有关，但SP在肌肉痛觉的感受和传递过程中的作用仍不明确。
研究者使用缺乏SP信号的小鼠来研究SP在肌肉痛觉敏感性中的作用。他们发现同SP信号正常的小鼠相比，缺乏SP信号的小鼠在接受了肌肉内注射酸性物质之后，对痛觉的敏感性增高，这与神经递质通常所起的兴奋性作用恰好相反。
导致该小鼠肌肉痛觉敏感性增高的原因，是其缺少SP信号基因并产生一些物质与SP受体结合。这一发现表明SP或许在肌肉痛觉传递中作为抑制剂通过抑制肌肉痛觉受体发挥作用，并作为抑制反馈通路的一部分在慢性肌肉痛患者身上起作用。
目前有一些通过减少纤维肌痛患者SP神经受体发挥作用的药物在进行临床试验，作者告诫这些研究人员须当心这类药物增加患者慢性肌肉痛以及肌肉痛觉敏感性的风险。（生物谷bioon.com）
doi:10.1073/pnas.1108903108
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An antinociceptive role for substance P in acid-induced chronic muscle pain
An antinociceptive role for substance P in acid-induced chronic muscle pain.
Release of substance P (SP) from nociceptive nerve fibers and activation of its receptor neurokinin 1 (NK1) are important effectors in the transmission of pain signals. Nonetheless, the role of SP in muscle pain remains unknown. Here we show that a single i.m. acid injection in mice lacking SP signaling by deletion of the tachykinin precursor 1 (Tac1) gene or coadministration of NK1 receptor antagonists produces long-lasting hyperalgesia rather than the transient hyperalgesia seen in control animals. The inhibitory effect of SP was found exclusively in neurons expressing acid-sensing ion channel 3, where SP enhances M-channel-like potassium currents through the NK1 receptor in a G protein-independent but tyrosine kinase-dependent manner. Furthermore, the SP signaling could alter action potential thresholds and modulate the expression of TTX-resistant sodium currents in medium-sized muscle nociceptors. Thus, i.m. SP mediates an unconventional NK1 receptor signal pathway to inhibit acid activation in muscle nociceptors, resulting in an unexpected antinociceptive effect against chronic mechanical hyperalgesia, here induced by repeated i.m. acid injection.
