Activation of Voltage-Gated KCNQ/Kv7 Channels by Anticonvulsant Retigabine Attenuates Mechanical Allodynia of Inflammatory Temporomandibular Joint in Rats

Molecular Pain - Tập 6 - Trang 1744-8069-6-49 - 2010
Wen Xu1, Yuwei Wu2, Yeping Bi1, Lei Tan1, Yehua Gan2, KeWei Wang1
1Department of Neurobiology, Neuroscience Research Institute, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China
2Center for TMD & Orofacial Pain, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Haidian District, Beijing 100081, China

Tóm tắt

Background: Temporomandibular disorders (TMDs) are characterized by persistent orofacial pain and have diverse etiologic factors that are not well understood. It is thought that central sensitization leads to neuronal hyperexcitability and contributes to hyperalgesia and spontaneous pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently the first choice of drug to relieve TMD pain. NSAIDS were shown to exhibit anticonvulsant properties and suppress cortical neuron activities by enhancing neuronal voltage-gated potassium KCNQ/Kv7 channels (M-current), suggesting that specific activation of M-current might be beneficial for TMD pain. Results: In this study, we selected a new anticonvulsant drug retigabine that specifically activates M-current, and investigated the effect of retigabine on inflammation of the temporomandibular joint (TMJ) induced by complete Freund's adjuvant (CFA) in rats. The results show that the head withdrawal threshold for escape from mechanical stimulation applied to facial skin over the TMJ in inflamed rats was significantly lower than that in control rats. Administration of centrally acting M-channel opener retigabine (2.5 and 7.5 mg/kg) can dose-dependently raise the head withdrawal threshold of mechanical allodynia, and this analgesic effect can be reversed by the specific KCNQ channel blocker XE991 (3 mg/kg). Food intake is known to be negatively associated with TMJ inflammation. Food intake was increased significantly by the administration of retigabine (2.5 and 7.5 mg/kg), and this effect was reversed by XE991 (3 mg/kg). Furthermore, intracerebralventricular injection of retigabine further confirmed the analgesic effect of central retigabine on inflammatory TMJ. Conclusions: Our findings indicate that central sensitization is involved in inflammatory TMJ pain and pharmacological intervention for controlling central hyperexcitability by activation of neuronal KCNQ/M-channels may have therapeutic potential for TMDs.

Từ khóa


Tài liệu tham khảo

10.1016/S1086-5802(16)30331-X

Sarlani E, 2004, J Orofac Pain, 18, 41

10.1016/j.tripleo.2004.11.014

10.14219/jada.archive.1996.0270

10.1159/000086200

10.1007/s11910-008-0053-7

10.1016/j.coms.2007.12.005

10.1016/j.pain.2006.08.028

10.1016/S0014-2999(02)02924-2

10.1523/JNEUROSCI.23-18-07227.2003

10.1007/s00210-004-0881-1

10.1016/j.ejphar.2004.01.017

10.1016/j.neulet.2006.11.043

10.1016/j.neuropharm.2008.04.006

10.1016/j.pain.2008.01.031

10.1016/S0304-3940(00)00866-1

10.1126/science.282.5395.1890

10.1038/sj.bjp.0703861

10.1016/S0028-3908(01)00029-6

10.1001/archneur.60.4.496

10.1016/S0079-6107(00)00004-3

10.1111/j.1528-1157.2000.tb01501.x

10.1111/j.1365-2842.2008.01863.x

10.1124/mol.104.007112

10.1152/jn.00631.2004

10.1523/JNEUROSCI.6323-09.2010

10.1016/S0031-9384(99)00136-5

10.1016/j.jsbmb.2005.05.013

10.1080/00016350600573183

10.1177/00220345000790091101

10.1016/S0091-3057(03)00072-8

10.1016/j.pain.2005.05.007

10.1016/j.neuroscience.2005.11.024

10.1111/j.1476-5381.2009.00111.x

10.1038/283673a0

10.1038/ng0198-53

10.1126/science.279.5349.403

10.1074/jbc.M003245200

10.1523/JNEUROSCI.21-24-09529.2001

10.1016/j.neulet.2006.02.017

10.1016/S0014-2999(97)01249-1

10.1038/nn1375

10.1016/0920-1211(95)00101-8

10.1016/0022-3913(89)90051-6

10.1016/0278-2391(91)90407-D

10.1016/S0278-2391(97)90526-7

10.1016/S0278-2391(98)90867-9

10.1097/01.ju.0000138155.33749.f4

Thông tin
Thông tin xuất bản

Molecular Pain

Tập 6

1744-8069-6-49

Thông tin tác giả