The Journal of neuroscience : the official journal of the Society for Neuroscience
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Sensory nerve fibers differ not only with respect to their sensory modalities and conduction velocities, but also in their relative roles for pain hypersensitivity. It is presently largely unknown which types of sensory afferents contribute to various forms of neuropathic and inflammatory pain hypersensitivity. Vesicular glutamate transporter 3-positive (VGluT3(+)) primary afferents, for example, have been implicated in mechanical hypersensitivity after inflammation, but their role in neuropathic pain remains under debate. ⋯ Further, we provide direct evidence that, despite not mediating painful stimuli in naive mice, activation of VGluT3(+) sensory fibers by light elicits pain behavior in the oxaliplatin but not the CCI model. Immunohistochemical and electrophysiological data support a role of transient receptor potential melastatin 8-mediated facilitation of synaptic strength at the level of the dorsal horn as an underlying mechanism. Together, we demonstrate that VGluT3(+) fibers contribute in an etiology-dependent manner to the development of mechano-cold hypersensitivity.