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

Yu Shin Kim, Yuxia Chu, Liang Han, Man Li, Zhe Li, Pamela Colleen LaVinka, Shuohao Sun, Zongxiang Tang, Kyoungsook Park, Michael J. Caterina, Ke Ren, Ronald Dubner, Feng Wei, Xinzhong Dong

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124 Scopus citations

Abstract

The peripheral terminals of primary nociceptive neurons play an essential role in pain detection mediatedby membrane receptors like TRPV1, a molecular sensor of heat and capsaicin. However, the contribution of central terminal TRPV1 in the dorsal hornto 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.

Original languageEnglish (US)
Pages (from-to)873-887
Number of pages15
JournalNeuron
Volume81
Issue number4
DOIs
StatePublished - Feb 19 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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    Kim, Y. S., Chu, Y., Han, L., Li, M., Li, Z., LaVinka, P. C., Sun, S., Tang, Z., Park, K., Caterina, M. J., Ren, K., Dubner, R., Wei, F., & Dong, X. (2014). Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. Neuron, 81(4), 873-887. https://doi.org/10.1016/j.neuron.2013.12.011