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Neuron. 2014 Feb 19;81(4):873-887. doi: 10.1016/j.neuron.2013.12.011. Epub 2014 Jan 23.

Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain.

Author information

Department of Neuroscience, Center of Sensory Biology, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Neural and Pain Sciences, Program in Neuroscience, Dental School, University of Maryland, Baltimore, Maryland 21201.
Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nanjing University of Chinese Medicine, Nanjing, China.
Department of Biological Chemistry, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Howard Hughes Medical Institute, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Contributed equally


The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediated by membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal horn to chronic pain has not been investigated directly. Combining primary sensory neuron-specific GCaMP3 imaging with a trigeminal neuropathic pain model, we detected robust neuronal hyperactivity in injured and uninjured nerves in the skin, soma in trigeminal ganglion, and central terminals in the spinal trigeminal nucleus. Extensive TRPV1 hyperactivity was observed in central terminals innervating all dorsal horn laminae. The central terminal TRPV1 sensitization was maintained by descending serotonergic (5-HT) input from the brainstem. Central blockade of TRPV1 or 5-HT/5-HT3A receptors attenuated central terminal sensitization, excitatory primary afferent inputs, and mechanical hyperalgesia in the territories of injured and uninjured nerves. Our results reveal central mechanisms facilitating central terminal sensitization underlying chronic pain.

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