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Characterisation of the nociceptive phenotype of suppressible galanin overexpressing transgenic mice

机译:可抑制甘丙肽过表达的转基因小鼠的伤害性表型的表征

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摘要

The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems and is involved in many diverse biological functions. There is a substantial data set that demonstrates galanin is upregulated after injury in the DRG, spinal cord and in many brain regions where it plays a predominantly antinociceptive role in addition to being neuroprotective and pro-regenerative. To further characterise the role of galanin following nerve injury, a novel transgenic line was created using the binary transgenic tet-off system, to overexpress galanin in galaninergic tissue in a suppressible manner. The double transgenic mice express significantly more galanin in the DRG one week after sciatic nerve section (axotomy) compared to WT mice and this overexpression is suppressible upon administration of doxycycline. Phenotypic analysis revealed markedly attenuated allodynia when galanin is overexpressed and an increase in allodynia following galanin suppression. This novel transgenic line demonstrates that whether galanin expression is increased at the time of nerve injury or only after allodynia is established, the neuropeptide is able to reduce neuropathic pain behaviour. These new findings imply that administration of a galanin agonist to patients with established allodynia would be an effective treatment for neuropathic pain.
机译:神经肽甘丙肽在中枢神经系统和外周神经系统中广泛表达,并参与许多不同的生物学功能。有大量数据表明,甘草肽在DRG,脊髓和许多大脑区域受伤后会上调,在这些区域中,甘丙肽除了具有神经保护作用和促进再生作用外,还起主要的伤害感受作用。为了进一步表征神经损伤后甘丙肽的作用,使用二元转基因tet-off系统创建了一种新的转基因品系,以可抑制的方式在丙氨酸能组织中过表达甘丙肽。与野生型小鼠相比,双转基因小鼠在坐骨神经切开后一周(脊髓切开术)在DRG中表达的甘丙肽含量显着高于野生型小鼠,这种过量表达在给予强力霉素后可被抑制。表型分析显示,当甘丙肽过表达时异常疼痛明显减弱,而甘丙肽抑制后异常疼痛增加。这种新颖的转基因品系表明,无论是在神经损伤时还是仅在异常性疼痛建立后,甘丙肽的表达就增加了,神经肽都能减少神经性疼痛行为。这些新发现暗示向已确定的异常性疼痛患者施用甘丙肽激动剂将是神经性疼痛的有效治疗方法。

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