Moss Andrew, Ingram Rachel, Koch Stephanie, Theodorou Andria, Low Lucie, Baccei Mark, Hathway Gareth J, Costigan Michael, Salton Stephen R, Fitzgerald Maria
UCL Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Mol Pain. 2008 Dec 10;4:62. doi: 10.1186/1744-8069-4-62.
The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated.
Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5-50 nmol) to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses.
VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.
神经营养因子调节多肽VGF在大鼠神经性疼痛的 spared 损伤模型中的作用已得到研究。该肽已被证明与海马体中的突触强化和学习有关，虽然已知外周神经损伤后背根神经节中的VGFmRNA会上调，但这种VGF肽在神经性疼痛中的作用尚未得到研究。
在受伤的背根神经节神经元、中枢终末及其靶背角神经元中观察到VGFmRNA和蛋白的长期上调。向未处理的大鼠鞘内注射VGF的C端活性部分TLQP-62（5-50 nmol）会导致长期的机械性和冷觉行为性异常性疼痛。在脊髓切片的全细胞膜片钳记录以及完整麻醉大鼠的感受野分析中证实了50 nM TLQP-62对背角神经元兴奋性的直接作用，其中VGF的显著作用是对自发活动和冷诱发反应。
因此，外周神经损伤后伤害性感受通路中的VGF表达受到高度调节，并且可以在未处理的动物中引起背角细胞兴奋和行为超敏反应。这些结果共同表明VGF在神经性疼痛中具有新的强大作用。
