Eugenol and lidocaine inhibit voltage-gated Na+ channels from dorsal root ganglion neurons with different mechanisms.

Eugenol (EUG) is a bioactive monoterpenoid used as an analgesic, preservative, and flavoring agent. Our new data show EUG as a voltage-gated Na+ channel (VGSC) inhibitor, comparable but not identical to lidocaine (LID). EUG inhibits both total and only TTX-R voltage-activated Na+ currents (INa) recorded from VGSCs naturally expressed on dorsal root ganglion sensory neurons in rats. Inhibition is quick, fully reversible, and dose-dependent. Our biophysical and pharmacological analyses showed that EUG and LID inhibit VGSCs with different mechanisms. EUG inhibits VGSCs with a dose-response relationship characterized by a Hill coefficient of 2, while this parameter for the inhibition by LID is 1. Furthermore, in a different way from LID, EUG modified the voltage dependence of both the VGSC activation and inactivation processes and the recovery from fast inactivated states and the entry to slow inactivated states. In addition, we suggest that EUG, but not LID, interacts with VGSC pre-open-closed states, according to our data.

State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated Na+ Channels by Anethole.

Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. Anethole is thought to carry out its biological activities through direct interaction with ion channels. Anethole is beneficial for neurodegenerative Alzheimer's and Parkinson's diseases. Nevertheless, nothing has been investigated regarding the effects of anethole on voltage-gated Na+ channels (VGSCs), which are major players in neuronal function. We used cultured dorsal root ganglion neurons from neonatal rats as a source of natively expressed VGSCs for electrophysiological studies using the whole-cell patch-clamp technique. Our data show that anethole interacts directly with VGSCs. Anethole quickly blocks and unblocks (when removed) voltage-activated Na+ currents in this preparation in a fully reversible manner. Anethole's binding affinity to these channels increases when the inactive states of these channels are populated, similar to lidocaine's effect on the same channels. Our data show that anethole inhibits neuronal activity by blocking VGSCs in a state-dependent manner. These findings relate to the putative anesthetic activity attributable to anethole, in addition to its potential benefit in neurodegenerative diseases.

Diabetes mellitus alters electrophysiological properties in neurons of superior cervical ganglion of rats.

Diabetic neuropathy is the most prevalent complication associated with diabetes mellitus (DM). The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. We investigated the changes in cellular electrophysiological properties and on Na+K+-ATPase activity of SCG neurons of rats with DM induced by streptozotocin (STZ). Three types of action potentials (AP) firing pattern were observed in response to a long (1 s) depolarizing pulse. Whilst some neurons fired a single AP (single firing phasic, SFP), others fired few APs (multiple firing phasic, MFP). A third type fired APs during more than 80% of the stimulus duration (tonic-like, TL). The occurrence of SFP, MFP and TL was 84.5, 13.8, and 1.7%, respectively. SFP and MFP differed significantly in their membrane input resistance (Rin). At the end of the 4th week of its time course, DM differently affected most types of neurons: DM induced depolarization of resting membrane potential (RMP), decreased AP amplitude in SFP, and decreased Rin in MFP. DM decreased spike after-hyperpolarization amplitude in MFP and the duration in SFP. Based on the RMP depolarization, we investigated the Na+K+-ATPase action and observed that DM caused a significant decrease in Na+K+-ATPase activity of SCG. In conclusion, we have demonstrated that DM affects several parameters of SCG physiology in a manner likely to have pathophysiological relevance.

Monoterpenoid terpinen-4-ol inhibits voltage-dependent Na+ channels of small dorsal root ganglia rat neurons.

The monoterpenoid terpinen-4-ol (4TERP) is known to inhibit cell excitability, has low toxicity and important pharmacological activities, which are likely related to neural excitability, such as anti-inflammatory, antiepileptic and antinociceptive effects. However, the pharmacological characteristics and mechanisms underlying the effects of 4TERP on blockade of neural action potential are not completely elucidated. Since Na+ current (INa) through voltage-dependent Na+ channels (NaV) is a major mechanism for excitability, the present study investigated the pharmacological characteristics and mechanisms of the action of 4TERP on INa through NaV. For this aim, dissociated small neurons of dorsal root ganglia of adult rats were used for whole cell patch-clamp recordings. 4TERP concentration-dependently inhibits INa (IC50 0.8 ±â€¯0.3 mM; pharmacological efficacy 42.89 ±â€¯5.54%). 4TERP interfered with INa through a mechanism with various components, which includes predominantly channel pore block and sensitivity to frequency of use. In presence of 4TERP (3 mM), decreasing stimulation from 5 Hz to very low frequency (75 s of quiescence previously to stimulation) induced INa decrease to 65.17 ±â€¯5.86% of control. 4TERP also altered (left shift) voltage sensitivity of the steady state activation of NaV. Data are discussed aiming to interpret the importance of blockade of INa through NaV as participant of 4TERP-induced inhibition of membrane excitability.

Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure.

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

Sialólito Gigante em Ducto de Wharton: um caso incomum / Giant Sialolith in the Wharton Duct: An Unusual Case

A obstrução das glândulas salivares por cálculos acomete 90% dessas estruturas, apresentando geralmente tamanho menor que 1 cm. É encontrada, principalmente, nas glândulas submandibulares. Clinicamente, o paciente apresenta um aumento de volume na região referente à glândula salivar envolvida, podendo apresentar sintomatologia dolorosa e drenagem purulenta. O presente artigo relata um caso de sialólito gigante com 2,5 cm de diâmetro, em glândula submandibular, removido cirurgicamente, com preservação funcional da glândula submandibular. O tratamento pode variar de acordo com o tamanho, a forma e localização do cálculo... (AU)

The obstruction of the salivary glands by calculations affects 90% of these structures, usually exhibiting a size smaller than 1 cm. It is mainly found in the submandibular glands. Clinically, the patient presents an increase in volume in the region related to the salivary gland involved and may present painful symptoms and purulent drainage. The present article reports a case of giant sialolith with a diameter of 2.5 cm in the submandibular gland, which was removed surgically with functional preservation of the submandibular gland. The treatment may vary according to the size, shape and location of the calculus... (AU)

Comparação dos resultados da fonoterapia e fonoterapia associada à acupuntura na paralisia facial periférica / Comparison between myofunctional therapy and myofunctional therapy associated with acupuncture on treatment for peripheral facial paralysis

OBJETIVO: comparar a eficácia da fonoterapia e da Acupuntura associada à fonoterapia em pacientes com paralisia facial periférica de Bell. MÉTODOS: foram encaminhados para tratamento fonoaudiológico 15 pacientes, dos quais oito foram selecionados randomicamente para fonoterapia associada à Acupuntura, constituindo o grupo experimental. Os dois grupos passaram por avaliação, seguida pelas sessões de tratamento e logo após foram reavaliados, por um examinador externo. Os dados foram analisados por testes de hipóteses com nível de significância de 5 por cento. RESULTADOS: a mediana do número de sessões foi de 12,0 para o grupo controle e 5,5 para o grupo experimental (p=0,007), sendo que todos os integrantes deste último receberam alta terapêutica. Das 10 variáveis correlacionadas à mobilidade, quatro (40,0 por cento) apresentaram melhora significante no grupo controle e sete (70,0 por cento) no grupo experimental. Em relação à tonicidade, das 11 variáveis analisadas verificou-se melhora em sete (63,6 por cento) no grupo submetido apenas à fonoterapia e em 11 (100,0 por cento) no grupo submetido à fonoterapia associada à Acupuntura. Quanto às 15 medidas faciais investigadas houve melhora nos dois grupos, sendo esta mais evidente no grupo experimental. Apenas uma variável (6,7 por cento) apresentou valor significante no que se refere àdiferença entre os dois grupos na reavaliação. Em contrapartida, na comparação entre a avaliação e a reavaliação verificou-se valores significantes em sete variáveis (46,7 por cento), sendo que em cinco (33,3 por cento) a melhora foi mais evidente no grupo experimental. CONCLUSÃO: a associação da terapia fonoaudiológica com a Acupuntura foi mais eficaz no tratamento da paralisia facial periférica de Bell, na amostra estudada.

PURPOSE: to compare the efficacy of speech-language therapy and acupuncture associated with speech-language therapy in patients with Bell's peripheral facial paralysis. METHODS: we referred 15 patients for speech-language therapy, of whom eight were randomly selected for speech-language therapy associated with acupuncture, making up the trial group. Both groups underwent an assessment, followed by treatment sessions and soon afterwards they were reassessed by an external examiner. Data were analyzed by hypothesis testing with a significance level of 5 percent. RESULTS: the median number of sessions was 12.0 for the control group and 5.5 for the trial group (p = 0.007), and all members of the latter were discharged from therapy. From the ten variables related to mobility, four (40.0 percent) showed significant improvement in the control group and seven (70.0 percent) in the trial group. Regarding tone, from the eleven variables there was improvement in seven (63.6 percent) in the group submitted only to speech-language therapy and in eleven (100.0 percent) in the group undergoing speech-language therapy associated with acupuncture. As for the 15 investigated facial measurements, there was an improvement in both groups, which was most evident in the trial group. Only one variable (6.7 percent) showed significant value in relation to the difference between the two groups in the reassessment. On the other hand, the comparison between the assessment and reassessment showed a significant variables in seven (46.7 percent), and in five (33.3 percent) the improvement was more evident in the trial group. CONCLUSION: the association of speech-language therapy with acupuncture was more effective in Bell' peripheral facial paralysis treatment, in the sample.

Effects of 1,8-cineole on electrophysiological parameters of neurons of the rat superior cervical ganglion.

1. 1,8-Cineole is a non-toxic small terpenoid oxide believed to have medicinal properties in folk medicine. It has been shown to have various pharmacological effects, including blockade of the compound action potential (AP). In the present study, using intracellular recording techniques, we investigated the effects of 1,8-cineole on the electrophysiological parameters of neurons of the superior cervical ganglion (SCG) in rats. 2. 1,8-Cineole (0.1-6 mmol/L) showed reversible and concentration-dependent effects on various electrophysiological parameters. At 3 and 6 mmol/L, but not at 0.1 and 1 mmol/L, 1,8-cineole significantly diminished the input resistance (R(i)) and altered the resting potential (E(m)) to more positive values. At 6 mmol/L, 1,8-cineole completely blocked all APs within 2.7 +/- 0.6 min (n = 12). In neurons exposed to 3 and 1 mmol/L 1,8-cineole, the effects regarding excitability varied from complete AP blockade to minor inhibition of AP parameters. The depolarization of E(m) and the decrease in R(i) induced by 6 mmol/L 1,8-cineole were unaltered by 200 micromol/L niflumic acid, a well known blocker of Ca(2+)-activated Cl(-) currents. 3. Significant correlations (Pearson correlation test) were found between changes in E(m) and decreases in AP amplitude (r = -0.893; P < 0.00282) and maximum ascendant inclination (r = -0.799; P < 0.0173), but not for maximum descendant inclination (r = 0.598; P < 0.117). Application of current to restore the transmembrane potential equal to control E(m) values in the presence of 6 mmol/L 1,8-cineole resulted in the partial recovery of AP. 4. The present study shows that 1,8-cineole effectively blocks the excitability of SCG neurons, probably through various mechanisms, one of which acts indirectly via depolarization of the neuronal cytoplasmatic membrane.