Selectively targeting pain in the trigeminal system.
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.
National Research Laboratory for Pain, Dental Research Institute and Department of Physiology School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea Department of Physiology School of Medicine, Hanyang University, Seoul 133-791, Republic of Korea Department of Oral Physiology and Neurobiology School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea Department of Anatomy and Cell Biology College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea Department of Neuroscience and Oral Physiology, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan Neural Plasticity Research Group, Massachusetts General Hospital & Harvard Medical School, Charlestown, MA 02129, USA Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Hyun Yeong
HY
Kim
Kihwan
K
Kim
Hai Ying
HY
Li
Gehoon
G
Chung
Chul-Kyu
CK
Park
Joong Soo
JS
Kim
Sung Jun
SJ
Jung
Min Kyung
MK
Lee
Dong Kuk
DK
Ahn
Se Jin
SJ
Hwang
Youngnam
Y
Kang
Alexander M
AM
Binshtok
Bruce P
BP
Bean
Clifford J
CJ
Woolf
Seog Bae
SB
Oh
D000200:Action Potentials / Q000187:drug effects*; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage; D004558:Electric Stimulation; D008012:Lidocaine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D050916:TRPV Cation Channels / Q000378:metabolism; D012668:Trigeminal Ganglion / Q000187:drug effects* / Q000503:physiopathology
D000779:Anesthetics, Local; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C012647:QX-314; D008012:Lidocaine; D002211:Capsaicin