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

Abstract

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.

• Authors: 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
• Journal: Neuron (Neuron) Vol. 81 Issue 4 Pg. 873-887 (Feb 19 2014) ISSN: 1097-4199 [Electronic] United States
• PMID: 24462040 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• TRPV Cation Channels
• TRPV1 protein, mouse
• Capsaicin

Topics

• Animals
• Capsaicin (pharmacology)
• Chronic Pain (drug therapy, genetics, metabolism)
• Disease Models, Animal
• Mice
• Mice, Inbred C57BL
• Neurons (drug effects, metabolism)
• Nociceptors (drug effects, metabolism)
• Spinal Cord (drug effects, metabolism)
• TRPV Cation Channels (metabolism)
• Trigeminal Ganglion (drug effects)