Kashiba H, Ueda Y, Senba E
Department of Physiology, Kansai College of Oriental Medicine, Osaka, Japan.
Neuroscience. 1997 Jan;76(1):299-312. doi: 10.1016/s0306-4522(96)00334-x.
While systemic capsaicin in adult rats is known to reduce substance P and somatostatin in primary sensory nerves, it is still unknown if it also affects the production of these peptides at the genetic level. Therefore, we examined the effects of systemically administered capsaicin on the expression of the beta-preprotachykinin, gamma-preprotachykinin, somatostatin, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, neuropeptide Y and neurotrophin receptor family (trkA, trkB, trkC) genes in dorsal root ganglion neurons by in situ hybridization in adult rats. Nerve growth factor is thought to be involved in the regulation of some of these genes. In the control animals, beta-preprotachykinin, gamma-preprotachykinin, calcitonin gene-related peptide, somatostatin, trkA, trkB and trkC messenger RNAs were found in about 30%, 30%, 40%, 10%, 40%, 5% and 20% of the lumbar dorsal root ganglion neurons, respectively. The number of neurons expressing beta/gamma-preprotachykinin and calcitonin gene-related peptide messenger RNAs decreased to about 50% and 70% of the control values, respectively, six days after subcutaneous administration of capsaicin (950 mg/kg). Simultaneously, the number of trkA messenger RNA-expressing neurons also decreased to about 70% of the control level, while the number of neurons expressing trkB and trkC messenger RNAs was unaffected. On the other hand, vasoactive intestinal polypeptide and galanin messenger RNAs, but not neuropeptide Y messenger RNA, began to be expressed in about 10% of dorsal root ganglion neurons after administration of capsaicin, although their messenger RNAs were not detected in the controls. However, the expression of somatostatin messenger RNA was unaffected by the systemic administration of capsaicin. The somatostatin messenger RNA was not co-expressed with vasoactive intestinal polypeptide and galanin messenger RNAs in the sensory neurons of rats given capsaicin. Electron microscopic analysis revealed a few degenerating unmyelinated afferents in sural nerves of the treated rats. The number of small-sized dorsal root ganglion cells labeled with Fluoro-Gold, a retrograde-tracing dye which was injected into the sural nerve of the treated rats, decreased to half of the control number. Our results suggest that systemic administration of capsaicin in adult rats depresses the expression of beta/gamma-preprotachykinin, calcitonin gene-related peptide and trkA messenger RNAs, and induces expression of vasoactive intestinal polypeptide and galanin messenger RNAs in sensory neurons, which may be due to the capsaicin-induced degeneration of a subpopulation of sensory afferents. We also demonstrated that the regulation of somatostatin gene expression in mature sensory neurons is not affected by systemic capsaicin.
虽然已知成年大鼠体内的全身性辣椒素会减少初级感觉神经中的P物质和生长抑素，但它是否也会在基因水平上影响这些肽的产生仍不清楚。因此，我们通过成年大鼠的原位杂交，研究了全身性给予辣椒素对背根神经节神经元中β-前速激肽原、γ-前速激肽原、生长抑素、降钙素基因相关肽、血管活性肠肽、甘丙肽、神经肽Y和神经营养因子受体家族（trkA、trkB、trkC）基因表达的影响。神经生长因子被认为参与了其中一些基因的调控。在对照动物中，分别在约30%、30%、40%、10%、40%、5%和20%的腰段背根神经节神经元中发现了β-前速激肽原、γ-前速激肽原、降钙素基因相关肽、生长抑素、trkA、trkB和trkC信使核糖核酸。皮下注射辣椒素（950毫克/千克）六天后，表达β/γ-前速激肽原和降钙素基因相关肽信使核糖核酸的神经元数量分别降至对照值的约50%和70%。同时，表达trkA信使核糖核酸的神经元数量也降至对照水平的约70%，而表达trkB和trkC信使核糖核酸的神经元数量未受影响。另一方面，给予辣椒素后，约10%的背根神经节神经元开始表达血管活性肠肽和甘丙肽信使核糖核酸，尽管在对照中未检测到它们的信使核糖核酸。然而，全身性给予辣椒素并未影响生长抑素信使核糖核酸的表达。在给予辣椒素的大鼠感觉神经元中，生长抑素信使核糖核酸未与血管活性肠肽和甘丙肽信使核糖核酸共表达。电子显微镜分析显示，处理过的大鼠腓肠神经中有一些退化的无髓传入神经。用逆行追踪染料Fluoro-Gold标记的小型背根神经节细胞数量，该染料注入处理过的大鼠腓肠神经后，降至对照数量的一半。我们的结果表明，成年大鼠全身性给予辣椒素会抑制β/γ-前速激肽原、降钙素基因相关肽和trkA信使核糖核酸的表达，并在感觉神经元中诱导血管活性肠肽和甘丙肽信使核糖核酸的表达，这可能是由于辣椒素诱导的感觉传入神经亚群的退化。我们还证明，成年感觉神经元中生长抑素基因表达的调控不受全身性辣椒素的影响。
