Selectively targeting pain in the trigeminal system

Hyun Yeong Kim; Kihwan Kim; Hai Ying Li; Gehoon Chung; Chul Kyu Park; Joong Soo Kim; Sung Jun Jung; Min Kyung Lee; Dong Kuk Ahn; Se Jin Hwang; Youngnam Kang; Alexander M. Binshtok; Bruce P. Bean; Clifford J. Woolf; Seog Bae Oh

doi:10.1016/j.pain.2010.02.016

Selectively targeting pain in the trigeminal system

Hyun Yeong Kim, Kihwan Kim, Hai Ying Li, Gehoon Chung, Chul Kyu Park, Joong Soo Kim, Sung Jun Jung, Min Kyung Lee, Dong Kuk Ahn, Se Jin Hwang, Youngnam Kang, Alexander M. Binshtok, Bruce P. Bean, Clifford J. Woolf, Seog Bae Oh^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Scopus citations

Abstract

We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (I_Na) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked I_Na and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain.

Original language	English
Pages (from-to)	29-40
Number of pages	12
Journal	Pain
Volume	150
Issue number	1
DOIs	https://doi.org/10.1016/j.pain.2010.02.016
State	Published - Jul 2010
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by Grant ( R0A-2008-000-20101-0 ) from National Research Laboratory Program and a Grant ( 2009K001256 ) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea . S.B.O was supported by Alice and Joseph Brooks Fund in the Department of Neurobiology, Harvard Medical School and LG Yonam Foundation during part of this work. Drs. Bean and Woolf are inventors on a filed patent related to targeting impermeant sodium channel blockers into nociceptors that has been licensed by Endo Pharmaceuticals from Harvard University.

Keywords

Action potentials
Local anesthetics
QX-314
TRPV1
Trigeminal system
Voltage-gated sodium channels

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10.1016/j.pain.2010.02.016

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title = "Selectively targeting pain in the trigeminal system",

abstract = "We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (INa) and action potentials (APs) in trigeminal ganglion (TG) neurons. However, co-application of QX-314 and capsaicin blocked INa and APs in TRPV1-positive TG and dental nociceptive neurons, but not in TRPV1-negative TG neurons or in small neurons from TRPV1 knock-out mice. Immunohistochemistry revealed that TRPV1 is not expressed by trigeminal motor and trigeminal mesencephalic neurons. Capsaicin had no effect on rat trigeminal motor and proprioceptive mesencephalic neurons and therefore should not allow QX-314 to enter these cells. Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain.",

keywords = "Action potentials, Local anesthetics, QX-314, TRPV1, Trigeminal system, Voltage-gated sodium channels",

author = "Kim, {Hyun Yeong} and Kihwan Kim and Li, {Hai Ying} and Gehoon Chung and Park, {Chul Kyu} and Kim, {Joong Soo} and Jung, {Sung Jun} and Lee, {Min Kyung} and Ahn, {Dong Kuk} and Hwang, {Se Jin} and Youngnam Kang and Binshtok, {Alexander M.} and Bean, {Bruce P.} and Woolf, {Clifford J.} and Oh, {Seog Bae}",

note = "Funding Information: This research was supported by Grant ( R0A-2008-000-20101-0 ) from National Research Laboratory Program and a Grant ( 2009K001256 ) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea . S.B.O was supported by Alice and Joseph Brooks Fund in the Department of Neurobiology, Harvard Medical School and LG Yonam Foundation during part of this work. Drs. Bean and Woolf are inventors on a filed patent related to targeting impermeant sodium channel blockers into nociceptors that has been licensed by Endo Pharmaceuticals from Harvard University. ",

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AU - Kim, Joong Soo

AU - Jung, Sung Jun

AU - Lee, Min Kyung

AU - Ahn, Dong Kuk

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AU - Kang, Youngnam

AU - Binshtok, Alexander M.

AU - Bean, Bruce P.

AU - Woolf, Clifford J.

AU - Oh, Seog Bae

N1 - Funding Information: This research was supported by Grant ( R0A-2008-000-20101-0 ) from National Research Laboratory Program and a Grant ( 2009K001256 ) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Education, Science and Technology, Republic of Korea . S.B.O was supported by Alice and Joseph Brooks Fund in the Department of Neurobiology, Harvard Medical School and LG Yonam Foundation during part of this work. Drs. Bean and Woolf are inventors on a filed patent related to targeting impermeant sodium channel blockers into nociceptors that has been licensed by Endo Pharmaceuticals from Harvard University.

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Selectively targeting pain in the trigeminal system

Abstract

Bibliographical note

Keywords

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