Identification of spinal circuits involved in touch-evoked dynamic mechanical pain
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CitationCheng, L., B. Duan, T. Huang, Y. Zhang, Y. Chen, O. Britz, L. Garcia-Campmany, et al. 2017. “Identification of spinal circuits involved in touch-evoked dynamic mechanical pain.” Nature neuroscience 20 (6): 804-814. doi:10.1038/nn.4549. http://dx.doi.org/10.1038/nn.4549.
AbstractMechanical hypersensitivity is a debilitating symptom associated with millions of chronic pain patients. It exists in distinct forms, including brush-evoked dynamic and filament-evoked punctate. Here we report that dynamic mechanical hypersensitivity induced by nerve injury or inflammation was compromised in mice with ablation of spinal VT3Lbx1 neurons defined by coexpression of VGLUT3Cre and Lbx1Flpo, as indicated by the loss of brush-evoked nocifensive responses and conditional place aversion. Electrophysiological recordings show that VT3Lbx1 neurons form morphine-resistant polysynaptic pathways relaying inputs from low-threshold Aβ mechanoreceptors to lamina I output neurons. Meanwhile, the subset of somatostatin (SOM) lineage neurons preserved in VT3Lbx1 neuron-ablated mice is largely sufficient to mediate von Frey filament-evoked punctate mechanical hypersensitivity, including both morphine-sensitive and morphine-resistant forms. Furthermore, acute silencing of VT3Lbx1 neurons attenuated pre-established dynamic mechanical hypersensitivity induced by nerve injury, suggesting these neurons as a potential cellular target for treating this form of neuropathic pain.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:34492288
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