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J Neurosci. 2019 May 31. pii: 2064-18. doi: 10.1523/JNEUROSCI.2064-18.2019. [Epub ahead of print]

Is Optogenetic Activation of Vglut1-positive Aβ Low-Threshold Mechanoreceptors Sufficient to Induce Tactile Allodynia in Mice after Nerve Injury?

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Department of Anesthesiology, Duke University School of Medicine
Department of Anesthesiology, Duke University School of Medicine.
Department of Neurobiology, Duke University School of Medicine.


Mechanical allodynia is a cardinal feature of pathological pain. Recent work has demonstrated the necessity of A[graphic1] low-threshold mechanoreceptors (Aβ-LTMRs) for mechanical allodynia-like behaviors in mice, but it remains unclear whether these neurons are sufficient to produce pain under pathological conditions. Thus, we generated a transgenic mouse in which channelrhodopsin-2 (ChR2) is conditionally expressed in Vesicular Glutamate Transporter 1 (Vglut1) sensory neurons (Vglut1-ChR2), which is a heterogeneous population of large-sized sensory neurons with features consistent with (A[graphic3]-LTMRs). In naive male Vglut1-ChR2 mice, transdermal hindpaw photostimulation evoked withdrawal behaviors in an intensity- and frequency-dependent manner, which were abolished by local anesthetic and also selective A-fiber blockade. Surprisingly, male Vglut1-ChR2 mice did not show significant differences in light-evoked behaviors or real-time aversion after nerve injury, despite marked hypersensitivity to punctate mechanical stimuli. Thus, we conclude that optogenetic activation of cutaneous Vglut1-ChR2 neurons alone is not sufficient to produce pain-like behaviors in neuropathic mice.Significance Statement: Mechanical allodynia, wherein innocuous touch is perceived as pain, is a common feature of pathological pain. To test the contribution of low-threshold mechanoreceptors to nerve injury-induced mechanical allodynia, we generated and characterized a new transgenic mouse (Vglut1-ChR2) to optogenetically activate cutaneous Vglut1-positive LTMRs. Using this mouse, we found that light-evoked behaviors were unchanged by nerve injury, which suggests that activation of Vglut1-positive LTMRs alone is not sufficient to produce pain. The Vglut1-ChR2 mouse will be broadly useful for the study of touch, pain and itch.

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