TY - JOUR
T1 - Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain
AU - Kim, Yu Shin
AU - Chu, Yuxia
AU - Han, Liang
AU - Li, Man
AU - Li, Zhe
AU - LaVinka, Pamela Colleen
AU - Sun, Shuohao
AU - Tang, Zongxiang
AU - Park, Kyoungsook
AU - Caterina, Michael J.
AU - Ren, Ke
AU - Dubner, Ronald
AU - Wei, Feng
AU - Dong, Xinzhong
PY - 2014/2/19
Y1 - 2014/2/19
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84896700036&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896700036&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2013.12.011
DO - 10.1016/j.neuron.2013.12.011
M3 - Article
C2 - 24462040
AN - SCOPUS:84896700036
VL - 81
SP - 873
EP - 887
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -