Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of α6 GABAA receptors.

γ-Aminobutyric acid type A (GABAA ) receptors containing the α6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK-I-56-1 at concentrations below 1 µM enhanced γ-aminobutyric acid (GABA) currents at recombinant rat α6ß3γ2, α6ß3δ and α6ß3 receptors, whereas it was inactive at most GABAA receptor subtypes containing other α subunits. DK-I-87-1 at concentrations below 1 µM was inactive at α6-containing receptors and only weakly modulated other GABAA receptors investigated. Both plasma and brain tissue kinetics of DK-I-56-1 were relatively slow, with half-lives of 6 and 13 hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10-300 nM throughout a 24-hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK-I-56-1 during 14 days after surgery or with DK-I-56-1 or DK-I-87-1 during 14 days after trigeminal neuropathy were already established, demonstrated that DK-I-56-1 but not DK-I-87-1 significantly reduced the hypersensitivity response to von Frey filaments. SIGNIFICANCE: Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK-I-56-1 that positively modulates α6 GABAA receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.

Apical root-end filling with tricalcium silicate-based cement in a patient with diabetes mellitus: A case report.

Introduction: The material used for root-end filling has to be biocompatible with adjacent periapical tissue and to stimulate its regenerative processes. Tricalcium silicate cement (TSC), as a new dental material, shows good sealing properties with dentin, high compression strengths and better marginal adaptation than commonly used root-end filling materials. Although optimal postoperative healing of periapical tissues is mainly influenced by characteristics of end-root material used, it could sometimes be affected by the influence of systemic diseases, such as diabetes mellitus (DM). Case report: We presented apical healing of the upper central incisor, retrofilled with TSC, in a diabetic patient (type 2 DM) with peripheral neuropathy. Standard root-end resection of upper central incisor was accompanied by retropreparation using ultrasonic retrotips to the depth of 3 mm and retrofilling with TSC. Post-operatively, the surgical wound healed uneventfully. However, the patient reported undefined dull pain in the operated area that could possibly be attributed to undiagnosed intraoral diabetic peripheral neuropathy, what was evaluated clinically. Conclusion: Although TSC presents a suitable material for apical root-end filling in the treatment of chronic periradicular lesions a possible presence of systemic diseases, like type 2 DM, has to be considered in the treatment outcome estimation.