Low-dose oral propranolol for treatment of thyrotoxic periodic paralysis with hypokalaemia in the emergency department: A case report.

WHAT IS KNOWN AND OBJECTIVE: Thyrotoxic periodic paralysis (TPP) with hypokalaemia is a rare acute phenomenon. Reports of the use of high-dose non-selective ß-blockers describe symptom resolution, but often administration does not occur promptly enough in the treatment course and patients may experience overcorrection and hyperkalaemia. CASE DESCRIPTION: A 37-year-old Hispanic male developed TPP. Patient was successfully treated with low-dose oral propranolol and potassium supplementation with no overcorrection. WHAT IS NEW AND CONCLUSION: Delay in the administration of non-selective ß-blockers may lead to overcorrection of potassium with exogenous supplementation. Low-dose propranolol administered in the Emergency Department was successful in preventing overcorrection of potassium.

Enhanced Percutaneous Delivery of Beta-Blockers Using Thermal Resurfacing Drug Delivery System for Topical Treatment of Infantile Hemangiomas.

BACKGROUND: Infantile hemangiomas (IHs) are the most common vascular tumors in children. In the past few years, topical beta-blockers (bBs) have been reported to be an effective treatment of superficial IHs. OBJECTIVE: We sought to evaluate the clinical effectiveness and safety profile of enhanced percutaneous delivery of bBs for the treatment of IH. METHODS: A retrospective study of all cases of IHs treated with enhanced percutaneous delivery of bBs between 2018 and 2019 was performed. Epidemiologic, clinical, and treatment data, including effectiveness score and safety, were reviewed. RESULTS: The study included 11 patients with a total of 11 IHs. Of the total number of IHs, 7 (63.7%) showed a good response to treatment and 4 (36.3%) had a partial response; thus all patients (100%) had good or partial response to treatment. No systemic or local adverse effects were reported. LIMITATIONS: This is an uncontrolled retrospective study. CONCLUSION: Enhanced percutaneous delivery of bBs is a safe and efficient topical therapy for IH.

Brain interstitial fluid drainage and extracellular space affected by inhalational isoflurane: in comparison with intravenous sedative dexmedetomidine and pentobarbital sodium.

Brain interstitial fluid drainage and extracellular space are closely related to waste clearance from the brain. Different anesthetics may cause different changes of brain interstitial fluid drainage and extracellular space but these still remain unknown. Herein, effects of the inhalational isoflurane, intravenous sedative dexmedetomidine and pentobarbital sodium on deep brain matters' interstitial fluid drainage and extracellular space and underlying mechanisms were investigated. When compared to intravenous anesthetic dexmedetomidine or pentobarbital sodium, inhalational isoflurane induced a restricted diffusion of extracellular space, a decreased extracellular space volume fraction, and an increased norepinephrine level in the caudate nucleus or thalamus with the slowdown of brain interstitial fluid drainage. A local administration of norepinephrine receptor antagonists, propranolol, atipamezole and prazosin into extracellular space increased diffusion of extracellular space and interstitial fluid drainage whilst norepinephrine decreased diffusion of extracellular space and interstitial fluid drainage. These findings suggested that restricted diffusion in brain extracellular space can cause slowdown of interstitial fluid drainage, which may contribute to the neurotoxicity following the waste accumulation in extracellular space under inhaled anesthesia per se.

Functional and neurometabolic asymmetry in SHR and WKY rats following vasoactive treatments.

A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and hypertensive rats has been described depending on the use of some vasoactive drugs and linked to certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection between the brain and physiologic parameters and metabolic factors from plasma and urine. To assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological parameters and metabolic factors from plasma and urine were determined using routine laboratory techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral pattern by changing the predominance of the correlations between peripheral parameters and central neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between SHR and WKY rats. These results support an asymmetric integrative function of the organism and suggest the possibility of a different neurometabolic response coupled to particular mood disorders, depending on the selected vasoactive drug.

Acupuncture at PC6 prevents cardiac hypertrophy in isoproterenol-treated mice.

OBJECTIVES: To investigate the effect of acupuncture at PC6 on cardiac hypertrophy in isoproterenol (ISO)-treated mice. METHODS: 48 male C57BL/6 mice underwent subcutaneous injection of ISO for 14 days and were randomly divided into four groups (n=12 each) that remained untreated (ISO group), received verum manual acupuncture (MA) treatment at PC6 (ISO+MA(PC6) group), sham MA at location on the tail not corresponding to any traditional acupuncture point (ISO+MA(tail) group), or propranolol (ISO+PR group). An additional 12 mice were given an injection of phosphate-buffered saline (PBS) and formed a healthy control (Normal) group. After performing echocardiography and measuring the ratio of heart weight (HW)/tibia length (TL) at 14 days, all mice were euthanased. Morphological examination was performed following haematoxylin and eosin and Masson's staining of heart tissues. Ultrastructural changes were observed by electron microscopy. Cardiac protein expression of atrial natriuretic peptide (ANP) and tumour necrosis factor α (TNFα) were measured by immunohistochemical (IHC) staining and Western blotting. RESULTS: Compared with the untreated model group, acupuncture at PC6 lowered the heart rate, reduced the ratio of HW/TL, improved the left ventricular (LV) anterior wall thickness (LVAWd), LV end-diastolic anterior wall thickness (LVAWs), LV end-systolic posterior wall thickness (LVPWd), LV end-diastolic posterior wall thickness (LVPWs), and fractional shortening (FS) as observed by echocardiography (ISO+MA(PC6) vs. ISO groups: P<0.05). Moreover, evidence from morphological studies demonstrated that acupuncture at PC6 inhibited myocardial hypertrophy and collagen deposition, and normalised the ultrastructural changes. In addition, ANP and TNFα expression were attenuated in the verum acupuncture group compared with the untreated model group (ISO+MA(PC6) vs. ISO groups: P<0.05). CONCLUSIONS: The results demonstrated that acupuncture at PC6 attenuates sympathetic overactivity. Additionally, it may improve cardiac performance by reversing adverse cardiac remodelling. Acupuncture has potential as a treatment for sympathetic hypertension.

Dangerous mistake: an accidental caffeine overdose.

Caffeine (1,3,7-trimethylxanthine) is a natural product commonly presented in food's composition, beverages and medicinal products. Generally, it is thought to be safe under normal dosage, yet it can be fatal in case of severe intoxication. We report a case of a healthy 32-year-old woman who went to the local emergency department (ED) 30 min after ingesting, accidentally, 5000 mg of anhydrous caffeine for a preworkout supplement. At the ED, she presented an episode of presyncope followed by agitation. ECG showed polymorphic broad complex QRS tachycardia and arterial blood gas revealed metabolic acidaemia with severe hypokalemia. The dysrhythmia was successfully treated with intravenous propranolol. Acid-base and hydroelectrolytic disorders were also corrected. A persistent sinus tachycardia was observed in the first 2 days in the ward and 5 days later she was discharged asymptomatic with internal medicine follow-up.

The role of propranolol as a radiosensitizer in gastric cancer treatment.

PURPOSE: The National Comprehensive Cancer Network guidelines indicate that radiotherapy in gastric cancer shows limited effectiveness at reducing the growth of gastric cancer. Therefore, enhancing the sensitivity and effect of radiotherapy with propranolol, a ß-adrenoceptor antagonist, could reduce tumor growth. The role of propranolol as a radiosensitizer has not been adequately studied; therefore, the purpose of the present study is to evaluate the effect of propranolol as a radiosensitizer against gastric cancer in vivo. METHODS: Sixty-four male nude mice bearing tumor xenografts were randomly divided into four groups. Cell culture was performed using the human gastric adenocarcinoma cell line SGC-7901. Mice with tumor xenografts were treated with propranolol, isoproterenol, and radiation. The data for tumor weight and volume were obtained for statistical analyses. Furthermore, the expression levels of COX-2, NF-κB, VEGF, and EGFR were examined using immunohistochemical techniques and Western blotting. RESULTS: The growth in the volume and weight of the tumor was lower in mouse models treated with propranolol and radiation therapy compared to the other groups. Decreased expression of NF-κB was also observed in treatment groups where both propranolol and radiation were used, leading to the reduction of COX-2, EGFR, and VEGF expression compared to that in the other groups. CONCLUSION: The present study indicated that propranolol potentiates the antitumor effects of radiotherapy in gastric cancer by inhibiting NF-κB expression and its downstream genes: VEGF, EGFR, and COX-2.

Efficacy of carvedilol versus propranolol versus variceal band ligation for primary prevention of variceal bleeding.

BACKGROUND AND AIMS: Band ligation and propranolol are the current therapies for primary prevention of variceal bleeding. Carvedilol is a rising nonselective beta-blocker used for reducing portal pressure with favorable outcome. The aim of this study to assess the efficacy of carvedilol, propranolol, and band ligation for primary prevention of variceal bleeding based on the effect of each regimen on progression of Child score and portal hypertensive gastropathy after 1 year. METHODS: The study included 264 cirrhotic patients with medium/large-sized varices who were candidates for primary prophylaxis of variceal bleeding. Patients were randomly divided into three groups: group I: band ligation; group II: propranolol; group III: carvedilol. RESULTS: Group I showed higher success rate of 75 %, followed by group III with 70.2 % and group II with 65.2 %. Risk of bleeding was comparable between the three groups, with group II carrying the highest rate of complications (34.7 %) followed by group III (14.2 %) and finally group I (5.7 %). After 1 year of follow-up, Child score did not improve in any of the studied groups, while portal hypertensive gastropathy significantly increased in group I but decreased in groups II and III. CONCLUSIONS: Band ligation is the best treatment option for primary prevention of variceal bleeding with minimal complications. Carvedilol is a good pharmaceutical alternative medicine to propranolol with lesser side-effects. Progress of liver disease as represented by Child score is not affected by any of the primary variceal prophylactic regimens, although medical treatment reduces portal hypertensive gastropathy. Choice of treatment depends on patient will, compliance with treatment, and endoscopist competence.

A Combination of Dexmedetomidine and Lidocaine Is a Cardiovascularly Safe Dental Local Anesthetic for Hypertensive Rats Treated With a Nonselective ß-Adrenergic Antagonist.

Hypertensive patients receiving nonselective ß-adrenergic antagonists are vulnerable to hypertension and bradycardia when injected with dental local anesthetic formulations containing epinephrine. Dexmedetomidine (DEX), an α2-adrenergic agonist, has been reported to prolong and enhance the local anesthetic effects of lidocaine. The cardiovascular effects of the DEX-lidocaine combination have not yet been investigated in the presence of nonselective ß-adrenergic antagonists. Therefore, we assessed the cardiovascular effects of the DEX-lidocaine combination in spontaneously hypertensive rats (SHR) treated with a nonselective ß-adrenergic antagonist (propranolol). We injected propranolol-treated rats with various concentrations of DEX alone, 100 µg/kg epinephrine alone, or 5 µg/kg DEX combined with 2% lidocaine and measured their blood pressure (BP) and heart rates (HR) to assess the cardiovascular effects. The BP of propranolol-treated SHR was significantly increased by treatment with 100 µg/kg epinephrine alone. The BP and HR of propranolol-treated SHR were not significantly changed by treatment with low concentrations of DEX, but they were significantly decreased by treatment with a high concentration of DEX (50 µg/kg). Moreover, there was no significant difference in the BP and HR of propranolol-treated SHR after the injection of a combination of 5 µg/kg DEX and 2% lidocaine. Thus, the DEX-lidocaine combination may be an acceptable addition to dental local anesthetic solutions from a cardiovascular standpoint for hypertensive patients receiving nonselective ß-adrenergic antagonists.

Thyrotoxic Channelopathies.

Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. Early recognition of TPP is vital to initiating appropriate treatment and to avoiding the risk of rebound hyperkalemia that may occur if high-dose potassium replacement is given. Here we present a case of 31 year old male with thyrotoxic periodic paralysis with diagnostic and therapeutic approach.

Desipramine administered chronically inhibits lipopolysaccharide-stimulated production of IL-1ß in the brain and plasma of rats.

Nowadays, it is assumed that therapeutic efficacy of antidepressants depends, at least partly, on their anti-inflammatory properties. The present study investigated for the first time the effect of 21-day oral administration of desipramine on the lipopolysaccharide (LPS)-stimulated IL-1ß concentration in the olfactory bulb, hypothalamus, frontal cortex, hippocampus and plasma of rats, and on the LPS-induced IL-1ß mRNA level in the olfactory bulb. Desipramine (15mg/kg/day) reduced significantly the LPS (250 µg/kg i.p.)-induced IL-1ß concentration in the olfactory bulb, hypothalamus and in plasma, and diminished the LPS effect on IL-1ß mRNA in the olfactory bulb. Plasma concentration of desipramine was comparable to its therapeutic range. By using the α1/α2-adrenoceptor antagonist prazosin and the unspecific ß-adrenoceptor antagonist propranolol given prior to LPS, we found that the effect of desipramine on LPS-induced IL-1ß production was partially mediated by both adrenoceptors in the olfactory bulb and plasma, and that ß-adrenoceptors contributed also to its effect on the stimulated IL-1ß concentration in the hypothalamus. The effect of LPS on the cerebral IL-1ß levels was, in part, mediated by ß-adrenoceptors and, in a region-specific manner, by α1/α2-adrenoceptors. The findings provide evidence for central and peripheral anti-inflammatory activity of desipramine and confirm the impact of the noradrenergic system on IL-1ß production induced by an immunostimulatory challenge.

Oral Propranolol as an Alternative Therapy for Orbital Angiolymphoid Hyperplasia With Eosinophilia.

An 8-year-old female patient presented with left upper eyelid swelling and erythema. Magnetic resonance imaging revealed an orbital mass involving the left lacrimal gland with subsequent incisional biopsy leading to the diagnosis of angiolymphoid hyperplasia with eosinophilia. Initially prescribed an oral corticosteroid, alternative management was sought after 4 months due to unwanted side effects of steroid therapy. Oral propranolol (2 mg/kg/day) was initiated with concurrent steroid taper. Interval decrease in lesion size was observed on subsequent magnetic resonance imaging with complete resolution of subjective symptoms (Fig. 1). She remains stable 14 months after starting beta-blocker therapy. To our knowledge, our case is the second case report suggesting oral beta-blocker may be an alternative therapy for orbital angiolymphoid hyperplasia with eosinophilia.

The effects of acute and preventive migraine therapies in a mouse model of chronic migraine.

Background The development of novel migraine therapies has been slow, in part because of the small number of clinically relevant animal models. We have recently developed a new mouse model of chronic migraine using chronic intermittent nitroglycerin, a known human migraine trigger. The objective of this study was to validate this model by testing known and potential migraine-preventive treatments. Methods Migraine therapies were administered to male and female mice for 11 days. On day 3, mice were tested with nitroglycerin every second day for nine days. Basal and nitroglycerin-evoked mechanical hypersensitivity was evaluated using von Frey filaments. Results Chronic intermittent nitroglycerin produced acute hyperalgesia with each administration, and progressive and sustained basal hypersensitivity. The established preventive migraine therapy propranolol effectively blocked the development of acute and chronic nitroglycerin-induced hyperalgesia, while valproate had no effect. Potential migraine-preventive therapies were also tested: Amiloride inhibited nitroglycerin-induced acute and chronic hyperalgesia; while memantine was ineffective. We also tested the acute migraine therapy sumatriptan, which did not alter nitroglycerin-induced hyperalgesia, but instead resulted in acute and chronic hyperalgesia similar to that observed following nitroglycerin administration. Conclusions This study establishes the chronic nitroglycerin model as an additional screening tool to test novel migraine-preventive therapies.

Propranolol combined with dopamine has a synergistic action in intensifying and prolonging cutaneous analgesia in rats.

BACKGROUND: The purpose of the experiment was to assess interactions of dopamine with propranolol as an infiltrative anesthetic. METHODS: After injecting the rats with four doses of drugs subcutaneously, the cutaneous analgesic effect of propranolol was compared with dopamine through the blockade of cutaneous trunci muscle reflex (CTMR) in response to local skin pinprick. Drug-drug interactions were examined via an isobolographic analysis. RESULTS: We demonstrated that the action of propranolol and dopamine was dose dependent to skin infiltrative analgesia. On the ED(50) (50% effective dose) basis, the rank of drug potency was propranolol (11.3 [10.6-12.2]µmol) > dopamine (195 [188-205]µmol) (p < 0.001). At the equi-anesthetic doses (ED(25), ED(50), ED(75)), the block duration caused by dopamine was equal to that caused by propranolol. Coadministration of dopamine and propranolol exhibited a synergistic effect on infiltrative cutaneous analgesia. CONCLUSIONS: The preclinical data showed that dopamine produced a lesser potency but a comparable duration of cutaneous analgesia compared to propranolol. Adding dopamine to propranolol potentiated and prolonged propranolol's cutaneous analgesic effect.

Effects of Prereactivation Propranolol on Cocaine Craving Elicited by Imagery Script/Cue Sets in Opioid-dependent Polydrug Users: A Randomized Study.

OBJECTIVES: Relapse to drug misuse may follow exposure to drug cues that elicit craving. The learned associations, or "emotional memories," that underlie responses to cues may be attenuated or erased by the ß-adrenergic antagonist propranolol during a "reconsolidation window" shortly after the memories are reactivated by cues. METHODS: We evaluated the effects of propranolol on cue-induced drug cravings in healthy opioid-dependent individuals who used cocaine while receiving methadone maintenance (n = 33). Participants were asked to recall specific cocaine use and neutral events in an interview; these events were used to develop personalized auditory script/cue sets. Approximately 1 week later, propranolol (40 mg) or placebo (random assignment, double blind) was administered orally before presentation of the script/cue sets; the presentation of the script/cue sets were tested 1 week and 5 weeks after the propranolol/placebo session. Ongoing drug use was monitored via urine screens and self-report in twice-weekly visits. RESULTS: Cue reactivity, as assessed by craving scales and physiological responses, was unexpectedly greater in the propranolol group than in the placebo group. This counterhypothesized group difference was present acutely during propranolol administration and seemed to persist (without reaching statistical significance) during the subsequent test sessions. CONCLUSIONS: Our results do not support the use of propranolol for cue-induced cocaine craving in opioid-maintained patients.

Formulation and process optimization of multiparticulate pulsatile system delivered by osmotic pressure-activated rupturable membrane.

In this study, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane (Eudragit(®) RS) via osmotic pressure (with NaCl as the osmogent) was developed and characterized for omeprazole, omeprazole sodium, and propranolol HCl which have different water solubilities. Multiparticulates in pellet form for incorporation with or without the osmogent were manufactured by three methods and then used to coat a polymeric membrane. Results demonstrated that drug/osmogent-containing pellets manufactured by the extrusion/spheronization method with incorporation of the osmogent were optimal. The lag time (tL) to initiate pulsatile release is regulated by tL=l(2)/(6×D), which is dependent on the coating levels (l(2)) and plasticizer content (D). The pulsatile release pattern was found to be dependent on the osmotic pressure (osmogent), drug solubility, and mechanical properties of the polymeric membrane (elasticity and toughness). Omeprazole with lower water solubility could not generate sufficient osmotic pressure to create a crack in the membrane to activate pulsatile release, whereas the two other model drugs with higher solubilities could. But adsorption of omeprazole sodium on Eudragit(®) RS via charge-charge interactions led the its incomplete release. Finally, with 4% osmogent of NaCl added, a lag time in a range from 0 to 12h proportionally regulated by varying both the membrane thickness and plasticizer level initiated the complete pulsatile release of propranolol HCl. In conclusion, a multiparticulate pulsatile drug delivery system activated by a rupturable controlled-release membrane via osmotic pressure was successfully developed, and clinical applications of chronotherapy with drugs like propranolol HCl are expected.

Formulation, characterization and clinical evaluation of propranolol hydrochloride gel for transdermal treatment of superficial infantile hemangioma.

The objective of the present study is to formulate and characterize propranolol hydrochloride (PPL · HCl) gel, and to evaluate the efficacy of this formulation in transdermal treatment for superficial infantile hemangioma (IH). The transdermal PPL · HCl gel was prepared by a direct swelling method, which chose hydroxypropyl methylcellulose (HPMC) as the matrix and used terpenes plus alcohols as permeation enhancer. Permeation studies of PPL · HCl were carried out with modified Franz diffusion cells through piglet skin. Our results pointed to that among all studied permeation enhancers, farnesol plus isopropanol was the most effective combination (Q24, 6027.4 ± 563.1 µg/cm(2), ER, 6.8), which was significantly higher than that of control gel (p < 0.05). High percutaneous penetration with related lower plasma drug level of PPL · HCl gel was confirmed by microdialysis technique in rats using the homemade PPL · HCl oral solution as a control. Clinical studies also confirmed the excellent therapeutic response and few side effects of the PPL · HCl gel. These results suggest that transdermal application of the PPL · HCl gel is an effective and safe formulation in treating superficial IH.

In vitro and in vivo evaluations of a novel pulsed and controlled osmotic pump capsule.

OBJECTIVE: For better treatment of circadian cardiovascular events, a novel Propranolol hydrochloride (PNH) delayed-release osmotic pump capsule was developed. METHODS: The capsule body was designed of asymmetric membrane and the capsule cap was made impermeable. The physical characteristics of capsule body walls and membrane permeability were compared among different coating solutions. RESULTS: The formulation with the glycerin and diethyl phthalate (DEP) ratio of 5:4 appeared to be the best. The lag time and subsequent drug release were investigated through assembling the capsule body with capsule caps of different length. WSR N-10 was chosen as the suspending for its moderate expanding capacity. The influence of factors (WSR N-10 content, NaCl content and capsule cap length) on the responses (lag time and drug release rate) was evaluated using central composite design-response surface methodology. A second-order polynomial equation was fitted to the data and actual response values were in good accordance with the predicted ones. The optimized formulation displayed complete drug delivery, zero-order release rate with 4-h lag time. The results of in vivo pharmacokinetics in beagle dogs clearly suggested the controlled and sustained release of PNH from the system and that the relative bioavailability of this preparation was about 1.023 comparing the marketed preparation. CONCLUSIONS: These results indicate that by the adjustment of capsule cap length, PNH could be developed as a novel pulsatile and controlled drug delivery system.

Evaluation of the noradrenergic pathway and alpha-2 and beta-receptors in the modulation of the analgesia induced by transcutaneous electric nerve stimulation of high and low frequencies / Evaluación de la vía noradrenérgica y de los receptores alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta y baja frecuencia / Avaliação da via noradrenérgica e dos receptores alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta e de baixa frequência

Transcutaneous electric nerve stimulation is a noninvasive method used in clinical Physiotherapy to control acute or chronic pain. Different theories have been proposed to explain the mechanism of the analgesic action of transcutaneous electric nerve stimulation, as the participation of central and peripheral neurotransmitters. The aim of this study was to evaluate the involvement of noradrenergic pathway and of the receptors alfa-2 and beta in the modulation of analgesia produced by transcutaneous electric nerve stimulation of high and low frequency in Wistar rats after chronic treatment with propranolol or yohimbine intraperitoneally. Animals weighing 200 to 300 g were divided into 9 groups (n=8), which were obtained nociceptive thresholds through the Tail Flick before and after application of TENS for comparing the change of pain. The administration of yohimbine or propranolol at a dose of 3 mg/kg was effective in antagonizing the analgesia induced by high (150 Hz) and low (10 Hz) frequency transcutaneous electric nerve stimulation according to ANOVA test followed by Duncan post hoc test (p<0.05). Thus, it is suggested the involvement of alpha-2 and beta noradrenergic receptors in the modulation of transcutaneous electric nerve stimulation-induced analgesia.

La estimulación eléctrica nerviosa transcutánea es un método no invasivo utilizado en la clínica de Fisioterapia para controlar el dolor agudo y crónico. Diversas teorías son propuestas para explanar el mecanismo de acción analgésico de la estimulación eléctrica nerviosa transcutánea, como la participación de neurotransmisores centrales y periféricos. El objetivo del presente estudio fue evaluar la participación de la vía noradrenérgica y de los receptores alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta y baja frecuencia en ratos del tipo Wistar, después del tratamiento crónico con yohimbina o propranolol por la vía intraperitoneal. Animales que pesaban 200 y 300 g fueron divididos en nueve grupos (n=8), por los cuales fueron obtenidos los umbrales nociceptivos por medio del Tail Flick, antes y después de la aplicación de la estimulación eléctrica nerviosa transcutánea con el intuito de comparar la alteración del cuadro álgico. La administración de yohimbina o propranolol en el dosis de 3 mg/kg fue eficaz en resultar en una antagonización de analgesia inducida por la estimulación eléctrica nerviosa transcutánea con alta (150 Hz) y baja (10 Hz) frecuencia, de acuerdo al test de ANOVA seguido del test post-hoc de Duncan (p>0,05). Por lo tanto, se sugiere el envolvimiento de los receptores noradrenergicos alfa-2 y beta en la modulación de analgesia inducida por la estimulación eléctrica nerviosa transcutánea.

Estimulação elétrica nervosa transcutânea é um método não invasivo utilizado na clínica de Fisioterapia para controlar dores aguda ou crônica. Diferentes teorias são propostas para explicar o mecanismo de ação analgésica da estimulação elétrica nervosa transcutânea, como a participação de neurotransmissores centrais e periféricos. O objetivo do presente estudo foi avaliar a participação da via noradrenérgica e dos receptores alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta e baixa frequência em ratos Wistar, após tratamento crônico com ioimbina ou propranolol por via intraperitoneal. Animais pesando entre 200 e 300 g foram divididos em 9 grupos (n=8), dos quais se obteve os limiares nociceptivos por meio do Tail Flick antes e após a aplicação da estimulação elétrica nervosa transcutânea para comparação de mudança do quadro álgico. A administração de ioimbina ou de propranolol na dose de 3 mg/kg foi efetiva em causar uma antagonização da analgesia induzida pela estimulação elétrica nervosa transcutânea de alta (150 Hz) e baixa frequência (10 Hz) segundo teste ANOVA seguido do teste post hoc Duncan (p<0,05). Dessa forma, sugere-se o envolvimento de receptores noradrenérgicos alfa-2 e beta na modulação da analgesia induzida pela estimulação elétrica nervosa transcutânea. .

Trauma reactivation plus propranolol is associated with durably low physiological responding during subsequent script-driven traumatic imagery.

OBJECTIVE: In a previous, double-blind, placebo-controlled study, patients with posttraumatic stress disorder (PTSD) showed lower physiological response during script-driven traumatic imagery 1 week after receiving a single dose of propranolol given after the retrieval of a traumatic memory. We hypothesized that this effect would extend beyond 1 week using a modified treatment approach. METHOD: Twenty-eight participants with PTSD read an account of their traumatic event once weekly for 6 consecutive weeks under the influence of open-label propranolol. One week and 4-months later, skin conductance, heart rate, and left corrugator electromyogram responses were measured while participants engaged in script-driven mental imagery of their traumatic event. Results from the 22 study participants were compared with results from treated and untreated participants in a previously published trial. RESULTS: Most participants in our study were classified as non-PTSD cases at posttreatment and follow-up according to a psychophysiological discriminant function analysis. Posttreatment skin conductance and heart rate responses of the current (propranolol-treated) participants were lower than those of placebo participants from the previous study. No difference was observed between physiological responding measured posttreatment and at follow-up. CONCLUSIONS: Low physiological responding during script-driven traumatic imagery after treatment extends up to 4 months, demonstrating the durability of the treatment effect's. Limitations include the absence of a placebo-controlled group and lack of physiological baseline measures. Despite these limitations, results point to the need for future trials examining the clinical efficacy of trauma reactivation plus propranolol, as it has the potential to become a novel, cost- and time-effective treatment for PTSD.