White D M, Mansfield K
Department of Anaesthesia and Pain Management, University of Sydney, N.S.W., Australia.
Neuroscience. 1996 Aug;73(3):881-7. doi: 10.1016/0306-4522(96)00055-3.
Recent studies suggest that rearrangement of synaptic circuitry of primary afferent neurons in the spinal cord may contribute, in part, to hyperalgesia that is often associated with peripheral nerve injury. This study of cultured adult rat dorsal root ganglion cells examined whether vasoactive intestinal polypeptide and neuropeptide Y, which are up-regulated in sensory neurons following nerve transection, possibly contribute to the morphological alterations induced by nerve injury. Neurite outgrowth of dissociated dorsal root ganglion cells was examined two weeks following either sciatic nerve transection or intrathecal administration of test agents via osmotic pumps. Dissociated cells taken from rats with transected sciatic nerve or following intrathecal administration of either vasoactive intestinal polypeptide or neuropeptide Y had a significant increase in the percentage of cells with neurites as compared to dorsal root ganglion cells taken from normal animals. Intrathecal administration, into rats with nerve lesion, of the vasoactive intestinal polypeptide and neuropeptide Y antagonists, vasoactive intestinal polypeptide(10-28) and alpha-trinositol, respectively, significantly attenuated the nerve injury-induced increase in neurite outgrowth. Vasoactive intestinal polypeptide and neuropeptide Y had no influence on neurite outgrowth when applied to normal dissociated dorsal root ganglion cells, however, when added to cells co-cultured with spinal cord explants, both peptides significantly increased the percentage of cells with neurites. K252a, a protein kinase inhibitor, attenuated the trophic action of neuropeptide Y, but not that of vasoactive intestinal polypeptide. The action of vasoactive intestinal polypeptide on neurite outgrowth was attenuated by the protein kinase A inhibitor, the Rp-isomer of adenosine-3',5'-cyclic monophosphorothioate. The results suggest that the peptides may contribute, indirectly, to the nerve injury-induced increase in neurite outgrowth of sensory neurons via separate spinally-derived neurotrophic factors and the study provides further insight into the possible mechanisms underlying hyperalgesia associated with nerve injury.
近期研究表明，脊髓初级传入神经元突触回路的重排可能在一定程度上导致了常与周围神经损伤相关的痛觉过敏。本研究对培养的成年大鼠背根神经节细胞进行了检测，以探究在神经横断后感觉神经元中上调的血管活性肠肽和神经肽Y是否可能导致神经损伤引起的形态学改变。在坐骨神经横断或通过渗透泵鞘内注射受试药物两周后，检测解离的背根神经节细胞的神经突生长情况。与取自正常动物的背根神经节细胞相比，取自坐骨神经横断大鼠或鞘内注射血管活性肠肽或神经肽Y后的大鼠的解离细胞中，有神经突的细胞百分比显著增加。分别向有神经损伤的大鼠鞘内注射血管活性肠肽拮抗剂血管活性肠肽(10 - 28)和神经肽Y拮抗剂α - 三肌醇，可显著减弱神经损伤诱导的神经突生长增加。将血管活性肠肽和神经肽Y应用于正常解离的背根神经节细胞时，对神经突生长没有影响，然而，当添加到与脊髓外植体共培养的细胞中时，这两种肽都显著增加了有神经突的细胞百分比。蛋白激酶抑制剂K252a减弱了神经肽Y的营养作用，但未减弱血管活性肠肽的营养作用。血管活性肠肽对神经突生长的作用被蛋白激酶A抑制剂腺苷 - 3',5'-环磷硫酰酯的Rp - 异构体减弱。结果表明，这些肽可能通过不同的脊髓源性神经营养因子间接促进神经损伤诱导的感觉神经元神经突生长增加，该研究进一步深入了解了与神经损伤相关的痛觉过敏的潜在机制。
