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

Research output: Contribution to journalArticle

103 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Central Nervous System Sensitization
Chronic Pain
Serotonin
Spinal Trigeminal Nucleus
Trigeminal Ganglion
Nociceptors
Capsaicin
Hyperalgesia
Carisoprodol
Neuralgia
Sensory Receptor Cells
Brain Stem
Hot Temperature
Pain
Skin
Membranes
TRPV1 receptor
Spinal Cord Dorsal Horn

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, Y. S., Chu, Y., Han, L., Li, M., Li, Z., LaVinka, P. C., ... 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

Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. / Kim, Yu Shin; Chu, Yuxia; Han, Liang; Li, Man; Li, Zhe; LaVinka, Pamela Colleen; Sun, Shuohao; Tang, Zongxiang; Park, Kyoungsook; Caterina, Michael J.; Ren, Ke; Dubner, Ronald; Wei, Feng; Dong, Xinzhong.

In: Neuron, Vol. 81, No. 4, 19.02.2014, p. 873-887.

Research output: Contribution to journalArticle

Kim, YS, Chu, Y, Han, L, Li, M, Li, Z, LaVinka, PC, Sun, S, Tang, Z, Park, K, Caterina, MJ, Ren, K, Dubner, R, Wei, F & Dong, X 2014, 'Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain', Neuron, vol. 81, no. 4, pp. 873-887. https://doi.org/10.1016/j.neuron.2013.12.011
Kim, Yu Shin ; Chu, Yuxia ; Han, Liang ; Li, Man ; Li, Zhe ; LaVinka, Pamela Colleen ; Sun, Shuohao ; Tang, Zongxiang ; Park, Kyoungsook ; Caterina, Michael J. ; Ren, Ke ; Dubner, Ronald ; Wei, Feng ; Dong, Xinzhong. / Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. In: Neuron. 2014 ; Vol. 81, No. 4. pp. 873-887.
@article{1b6dcdf93ba14741a5967b803beb26d8,
title = "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 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.",
author = "Kim, {Yu Shin} and Yuxia Chu and Liang Han and Man Li and Zhe Li and LaVinka, {Pamela Colleen} and Shuohao Sun and Zongxiang Tang and Kyoungsook Park and Caterina, {Michael J.} and Ke Ren and Ronald Dubner and Feng Wei and Xinzhong Dong",
year = "2014",
month = "2",
day = "19",
doi = "10.1016/j.neuron.2013.12.011",
language = "English (US)",
volume = "81",
pages = "873--887",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",

}

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

VL - 81

SP - 873

EP - 887

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 4

ER -