Selectively targeting pain in the trigeminal system

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

doi:10.1016/j.pain.2010.02.016

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Volume 150, Issue 1 , Pages 29-40, July 2010

Selectively targeting pain in the trigeminal system

Hyun Yeong Kim
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Kihwan Kim
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Hai Ying Li
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Gehoon Chung
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Chul-Kyu Park
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Joong Soo Kim
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
Sung Jun Jung
- Department of Physiology School of Medicine, Hanyang University, Seoul 133-791, Republic of Korea
Min Kyung Lee
- Department of Oral Physiology and Neurobiology School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea
Dong Kuk Ahn
- Department of Oral Physiology and Neurobiology School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea
Se Jin Hwang
- Department of Anatomy and Cell Biology College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea
Youngnam Kang
- Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan
Alexander M. Binshtok
- Neural Plasticity Research Group, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA
Bruce P. Bean
- Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA
Clifford J. Woolf
- Neural Plasticity Research Group, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA
Seog Bae Oh
- National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea
- Corresponding author. Address: Department of Physiology, School of Dentistry, Seoul National University, 28-2 Yeongeon-Dong, Chongno-Ku, Seoul 110-749, Republic of Korea. Tel.: +82 2 740 8656; fax: +82 2 7625107.

Received 21 August 2009; received in revised form 5 December 2009; accepted 9 February 2010. published online 17 March 2010.

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.

Abbreviations: APs, action potentials, CNS, central nervous system, dEMG, digastric electromyogram, DiI, 1,1′-dioctadecyl-3,3,3′′3′-teramethylindo-carbocyanine perchlorate, DRG, dorsal root ganglia, I_Na, voltage-gated sodium channel currents, LAs, local anesthetics, TG, trigeminal ganglion, TRPV1, transient receptor potential vanilloid 1, VGSCs, voltage-gated sodium channels, Vmes, trigeminal mesencephalic nucleus, Vmot, trigeminal motor nucleus, V_rest, resting membrane potential