|Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats|
|Xu, Wen1; Wu, Yuwei2,3; Bi, Yeping1; Tan, Lei1; Gan, Yehua2,3; Wang, KeWei1|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Neurosciences & Neurology|
|关键词[WOS]||TRIGEMINAL ROOT GANGLION ; POTASSIUM CHANNELS ; MOUSE-BRAIN ; PAIN ; EXCITABILITY ; CURRENTS ; OPENER ; SUBUNITS ; THERAPY ; NEURONS|
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.
|项目编号||30630017 ; 30970919 ; 2007CB512100 ; B07001|
|资助机构||National Science Foundation of China ; Ministry of Science Technology of China ; Ministry of Education of China|
|作者单位||1.Peking Univ, Hlth Sci Ctr, Neurosci Res Inst, Dept Neurobiol, Beijing 100191, Peoples R China|
2.Peking Univ, Sch Stomatol, Ctr TMD & Orofacial Pain, Beijing 100081, Peoples R China
3.Peking Univ, Hosp Stomatol, Ctr TMD & Orofacial Pain, Beijing 100081, Peoples R China
|Xu, Wen,Wu, Yuwei,Bi, Yeping,et al. Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats[J]. MOLECULAR PAIN,2010,6(1).|
|APA||Xu, Wen,Wu, Yuwei,Bi, Yeping,Tan, Lei,Gan, Yehua,&Wang, KeWei.(2010).Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats.MOLECULAR PAIN,6(1).|
|MLA||Xu, Wen,et al."Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats".MOLECULAR PAIN 6.1(2010).|
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