Activation of voltage-gated KCNQ/Kv7 channels by anticonvulsant retigabine attenuates mechanical allodynia of inflammatory temporomandibular joint in rats

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

Similarities and differences of estrogen in the regulation of temporomandibular joint osteoarthritis and knee osteoarthritis

Background. Temporomandibular joint osteoarthritis (TMJOA) and knee osteoarthritis (knee OA) are two kinds of common osteoarthritis (OA) that are characterized by chronic degeneration of soft and hard tissues around joints. Their gender and age differences suggest that there are similarities and differences between the pathogenic mechanisms of TMJOA and knee OA. Objective. To review recent studies on the effect of estrogen on TMJOA and knee OA, and summarize their possible pathogenesis and molecular mechanisms. Sources. Articles up to present reporting the relationship of estrogen and TMJOA or knee OA are included. An extensive electronic search was conducted of databases including PubMed, Web of science core collection. Conclusion. According to epidemiological investigations, TMJOA primarily happens to females of puberty and childbearing age, while knee OA mainly affects postmenopausal women. Epidemiological investigation and experimental research suggest that estrogen may have a different effect on TMJ and on knee. Though estrogen regulates TMJOA and knee OA via estrogen-related receptors (ERR), their pathogenesis and pathway of estrogen regulation are different. To find out the accurate regulation of estrogen on TMJOA and knee OA, specific pathways and molecular mechanisms still need further exploration