Seal Rebecca P, Wang Xidao, Guan Yun, Raja Srinivasa N, Woodbury C Jeffery, Basbaum Allan I, Edwards Robert H
Department of Physiology, University of California, San Francisco School of Medicine, California 94143, USA.
Nature. 2009 Dec 3;462(7273):651-5. doi: 10.1038/nature08505. Epub 2009 Nov 15.
Mechanical pain contributes to the morbidity associated with inflammation and trauma, but primary sensory neurons that convey the sensation of acute and persistent mechanical pain have not been identified. Dorsal root ganglion (DRG) neurons transmit sensory information to the spinal cord using the excitatory transmitter glutamate, a process that depends on glutamate transport into synaptic vesicles for regulated exocytotic release. Here we report that a small subset of cells in the DRG expresses the low abundance vesicular glutamate transporter VGLUT3 (also known as SLC17A8). In the dorsal horn of the spinal cord, these afferents project to lamina I and the innermost layer of lamina II, which has previously been implicated in persistent pain caused by injury. Because the different VGLUT isoforms generally have a non-redundant pattern of expression, we used Vglut3 knockout mice to assess the role of VGLUT3(+) primary afferents in the behavioural response to somatosensory input. The loss of VGLUT3 specifically impairs mechanical pain sensation, and in particular the mechanical hypersensitivity to normally innocuous stimuli that accompanies inflammation, nerve injury and trauma. Direct recording from VGLUT3(+) neurons in the DRG further identifies them as a poorly understood population of unmyelinated, low threshold mechanoreceptors (C-LTMRs). The analysis of Vglut3(-/-) mice now indicates a critical role for C-LTMRs in the mechanical hypersensitivity caused by injury.
机械性疼痛会导致与炎症和创伤相关的发病率，但传递急性和持续性机械性疼痛感觉的初级感觉神经元尚未被确定。背根神经节（DRG）神经元利用兴奋性递质谷氨酸将感觉信息传递到脊髓，这一过程依赖于谷氨酸转运到突触小泡中以便进行调节性胞吐释放。在此，我们报告DRG中的一小部分细胞表达低丰度的囊泡谷氨酸转运体VGLUT3（也称为SLC17A8）。在脊髓背角，这些传入纤维投射到I层和II层的最内层，而此前认为这两层与由损伤引起的持续性疼痛有关。由于不同的VGLUT亚型通常具有非冗余的表达模式，我们使用Vglut3基因敲除小鼠来评估VGLUT3(+)初级传入纤维在对体感输入的行为反应中的作用。VGLUT3的缺失特异性地损害了机械性疼痛感觉，尤其是对伴随炎症、神经损伤和创伤的通常无害刺激的机械性超敏反应。对DRG中VGLUT3(+)神经元的直接记录进一步将它们确定为一群尚未被充分了解的无髓鞘、低阈值机械感受器（C-LTMRs）。对Vglut3(-/-)小鼠的分析现在表明C-LTMRs在由损伤引起的机械性超敏反应中起关键作用。
