Neurophysiologic assessment of small fibre damage in chemotherapy-induced peripheral neuropathy.

OBJECTIVE: In patients with chemotherapy-induced peripheral neuropathy (CIPN), demonstration of small fibre (SF) damage is important to understand chronic late effects. METHODS: Thirty patients having complaints compatible with possible CIPN following treatment with oxaliplatin or docetaxel were compared with 27 healthy subjects. All subjects were evaluated with quantitative sensory testing (QST) assessing SF function and laser evoked potentials (LEP). In addition, SF-damage was assessed using cutaneous silent periods evoked with electrical (El-CSP) and laser (Ls-CSP) stimuli. RESULTS: For LEP, N2P2 amplitudes were significantly smaller in patients than controls in both upper (P = 0.007) and lower extremities (P = 0.002), and the N1 amplitude in upper extremities of patients were significantly smaller than in controls (P = 0.001). SF-QST, LEP, Ls-CSP, and El-CSP were abnormal in 10 (33.3%), 16 (53.3%), 19 (63.3%), and 24 (80%) of CIPN patients, respectively. CONCLUSIONS: In patients with possible CIPN, El-CSP and Ls-CSP were more often abnormal than LEP and QST. This is probably because El-CSP and Ls-CSP inform mainly about peripheral nociceptive fibres, while LEP and QST inform about peripheral and central nociceptive pathways together. SIGNIFICANCE: LEP and QST are established methods to detect SF-damage. El- and Ls-CSP might help clinicians in diagnosing SF-damage.

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury.

Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.

Comparison of preseptal and pretarsal onabotulinum toxin an injection in patients with hemifacial spasm.

AIM: The aim of the present study was to evaluate the effects of different doses of onabotulinum toxin A on the amplitude and latency values of the blink reflex and facial nerve in the pretarsal and preseptal portions of the orbicularis oculi muscle in patients with hemifacial spasm. MATERIALS AND METHODS: Thirty patients with hemifacial spasm were assigned in two equal groups: Pretarsal Group: Five units of onabotulinum toxin A were injected into each of 2 points of the pretarsal portion; Preseptal Group: Five units of onabotulinum toxin A was injected into 4 points of the preseptal portion. We compared the electromyographic features of the patients before and 5 weeks after botulinum toxin (BTX) injection. RESULTS: In comparison of pre- and post-treatment measurements of blink reflex amplitude responses, the decreases in R1 (p = 0.003), R2 (p < 0.001), and R2C amplitudes (p = 0.031) were found to be significant in the BTX injected side in the pretarsal group. In the comparison of pre- and post-treatment measurements of facial nerve compound action potential amplitude changes, decreases in the amplitudes of the BTX injected (ipsilateral), and uninjected (contralateral) side in the pretarsal group were found to be significant (p < 0.001 for both groups). Decreases in the amplitudes of the BTX injected, and uninjected side in the preseptal group were found to be significant (p < 0.001, and p = 0.008, respectively). CONCLUSION: According to our hypothesis, the smaller amount of BTX applied to the pretarsal portion was found to be more effective than higher amount of BTX injected into the preseptal portion of the orbicularis oculi muscle.

Performance of blink reflex in patients during anesthesia induction with propofol and remifentanil: prediction probabilities and multinomial logistic analysis.

BACKGROUND: The amount of propofol needed to induce loss of responsiveness varied widely among patients, and they usually required less than the initial dose recommended by the drug package inserts. Identifying precisely the moment of loss of responsiveness will determine the amount of propofol each patient needs. Currently, methods to decide the exact moment of loss of responsiveness are based on subjective analysis, and the monitors that use objective methods fail in precision. Based on previous studies, we believe that the blink reflex can be useful to characterize, more objectively, the transition from responsiveness to unresponsiveness. The purpose of this study is to investigate the relation between the electrically evoked blink reflex and the level of sedation/anesthesia measured with an adapted version of the Richmond Agitation-Sedation Scale, during the induction phase of general anesthesia with propofol and remifentanil. Adding the blink reflex to other variables may allow a more objective assessment of the exact moment of loss of responsiveness and a more personalized approach to anesthesia induction. RESULTS: The electromyographic-derived features proved to be good predictors to estimate the different levels of sedation/anesthesia. The results of the multinomial analysis showed a reasonable performance of the model, explaining almost 70% of the adapted Richmond Agitation-Sedation Scale variance. The overall predictive accuracy for the model was 73.6%, suggesting that it is useful to predict loss of responsiveness. CONCLUSIONS: Our developed model was based on the information of the electromyographic-derived features from the blink reflex responses. It was able to predict the drug effect in patients undergoing general anesthesia, which can be helpful for the anesthesiologists to reduce the overwhelming variability observed between patients and avoid many cases of overdosing and associated risks. Despite this, future research is needed to account for variabilities in the clinical response of the patients and with the interactions between propofol and remifentanil. Nevertheless, a method that could allow for an automatic prediction/detection of loss of responsiveness is a step forward for personalized medicine.

Efecto del bloqueo neuromuscular sobre la monitorización biespectral en los niños críticamente enfermos / Effect of neuromuscular blockade on the bispectral index in critically ill patients

INTRODUCCIÓN: Estudios previos sugieren que el bloqueo neuromuscular (BNM) altera la monitorización del índice biespectral (BIS) en los niños sedados. El objetivo fue analizar la repercusión del uso y suspensión del BNM en la monitorización BIS en niños críticamente enfermos. MÉTODOS: Estudio observacional prospectivo. Se incluyeron los niños que recibían perfusiones intravenosas de vecuronio con monitorización BIS. Se analizaron variables clínicas, diagnósticas, hemodinámicas, sedoanalgesia y relajantes musculares y parámetros del BIS. Se compararon los valores del BIS antes del uso de relajantes neuromusculares, durante su administración, antes de su retirada y durante las 24 h siguientes a su suspensión. RESULTADOS: Treinta y cinco pacientes (edad mediana 30 meses). El diagnóstico más frecuente fue cardiopatía (85%). Las indicaciones más frecuentes para iniciar relajantes neuromusculares fueron bajo gasto cardiaco (45%) y adaptación a ventilación mecánica (20%). El BNM no produjo cambios significativos en los valores del BIS. Se observó una disminución de los valores del electromiograma a las 6 h (34,9 ± 9,4 vs. 31,2 ± 7; p = 0,008) y a las 12 h del inicio de la perfusión de vecuronio (34,9 ± 9,4 vs. 28,6 ± 4,8; p = 0,006). Tras retirar el vecuronio hubo un ligero aumento significativo del BIS (de 42,7 ± 11 a 48,4 ± 14,5, p = 0,001), así como en las siguientes 6 y 12 h (51,3 ± 16,6; p = 0,015). No hubo diferencias en las dosis de sedantes o analgésicos, excepto del fentanilo, que fue disminuido tras retirar el vecuronio. CONCLUSIÓN: El BNM continuo produce pequeños cambios en los valores del BIS sin relevancia clínica, y no altera la monitorización del nivel de conciencia del BIS en los niños críticamente enfermos

INTRODUCTION: It has been suggested that neuromuscular blockade (NMB) affects the capacity of bispectral index (BIS) monitoring to measure consciousness in sedated children. Our aim was to analyse the impact of NMB on BIS values in critically ill children. METHODS: We conducted a prospective observational study of children monitored with a BIS system that received a continuous infusion of vecuronium. We analysed data on clinical, diagnostic and haemodynamic variables, sedatives, analgesics, muscle relaxants, and BIS parameters. We compared BIS parameters before the use of a muscle relaxant, during its administration, before its discontinuation and for the 24hours following the end of the infusion. RESULTS: The analysis included 35 patients (median age, 30 months). The most common diagnosis was heart disease (85%). The most frequent indication for initiation of NMB was low cardiac output (45%), followed by adaptation to mechanical ventilation (20%). Neuromuscular blockade did not produce a significant change in BIS values. We found a decrease was observed in electromyography values at 6hours (34.9 ± 9.4 vs. 31.2 ± 7; P=.008) and 12hours after initiation of NMB (34.9 ± 9.4 vs. 28.6 ± 4.8; P=.006). We observed a small significant increase in BIS after discontinuation of NMB (from 42.7 ± 11 to 48.4 ± 14.5, P=.001), and 6 and 12hours later (51.3 ± 16.6; P=.015). There were no differences in the doses of sedatives or analgesics except for fentanyl, of which the dose was lowered after discontinuation of vecuronium. CONCLUSION: Continuous NMB produces small changes on BIS values that are not clinically significant and therefore does not interfere with BIS consciousness monitoring in critically ill children

Verification and Defined Dosage of Sodium Pentobarbital for a Urodynamic Study in the Possibility of Survival Experiments in Female Rat.

OBJECTIVES: To evaluate the effects of pentobarbital dosages on lower urinary tract function and to define an appropriate dosage of sodium pentobarbital that would be suitable for urodynamic studies in which recovery from anesthesia and long term survive were needed for subsequent experiment. METHODS: Twenty-four 8-week-old, female, virgin, Sprague-Dawley rats (200-250 g) were used in this study. Rats in study groups received gradient doses of pentobarbital intraperitoneally, and those in the control group received urethane intraperitoneally. External urethral sphincter electromyography (EUS-EMG) was recorded simultaneously during cystometry and leak point pressure tests. The toe-pinch reflex was used to determine the level of anesthesia. RESULTS: Micturition was normally induced in both the urethane group and 32 mg/kg pentobarbital group. However, in groups of 40 mg/kg or 36 mg/kg pentobarbital, micturition failed to be induced; instead, nonvoiding contractions accompanied by EUS-EMG tonic activity were observed. There were no significant differences in leak point pressure or EUS-EMG amplitude or frequency between the urethane and 32 mg/kg pentobarbital groups. CONCLUSIONS: This study confirmed significant dose-dependent effects of pentobarbital on lower urinary tract function and 32 mg/kg pentobarbital as an appropriate dosage for recovery urodynamic testing, which enable the achievement of expected essential micturition under satisfactory anesthesia in female rats.

Contribution of 5-HT2 Receptors to the Control of the Spinal Locomotor System in Intact Rats.

Applying serotonergic (5-HT) agonists or grafting of fetal serotonergic cells into the spinal cord improves locomotion after spinal cord injury. Little is known about the role of 5-HT receptors in the control of voluntary locomotion, so we administered inverse agonists of 5-HT2 (Cyproheptadine; Cypr), 5-HT2A neutral antagonist (Volinanserin; Volin), 5-HT2C neutral antagonist (SB 242084), and 5-HT2B/2C inverse agonist (SB 206553) receptors intrathecally in intact rats and monitored their effects on unrestrained locomotion. An intrathecal cannula was introduced at the low thoracic level and pushed caudally until the tip reached the L2/L3 or L5/L6 spinal segments. Locomotor performance was evaluated using EMG activity of hindlimb muscles during locomotion on a 2 m long runway. Motoneuron excitability was estimated using EMG recordings during dorsi- and plantar flexion at the ankle. Locomotion was dramatically impaired after the blockage of 5-HT2A receptors. The effect of Cypr was more pronounced than that of Volin since in the L5/L6 rats Cypr (but not Volin) induced significant alteration of the strength of interlimb coordination followed by total paralysis. These agents significantly decreased locomotor EMG amplitude and abolished or substantially decreased stretch reflexes. Blocking 5-HT2B/2C receptors had no effect either on locomotion or reflexes. We suggest that in intact rats serotonin controls timing and amplitude of muscle activity by acting on 5-HT2A receptors on both CPG interneurons and motoneurons, while 5-HT2B/2C receptors are not involved in control of the locomotor pattern in lumbar spinal cord.

Effects of neuromuscular blockade reversal on bispectral index and frontal electromyogram during steady-state desflurane anesthesia: a randomized trial.

The degree of neuromuscular blockade reversal may affect bispectral index (BIS) value. One possible reason is that the reverse of neuromuscular blockade affects electromyographic (EMG) signals of fascial muscle. Another reason is, the afferentation theory, the reverse of neuromuscular blockade relieves block signals generated in muscle stretch receptors from accessing the brain through afferent nerve pathways and induces arousal. Inaccurate BIS value may lead to overdose of drugs or the risk of intraoperative awareness. We compared changes in BIS and EMG values according to neuromuscular blockade reversal agents under steady-state desflurane anesthesia. A total of 65 patients were randomly allocated to receive either neostigmine 0.05 mg/kg, sugammadex 4 mg/kg, or pyridostigmine 0.25 mg/kg for neuromuscular blockade reversal under stable desflurane anesthesia, and 57 patients completed the study. The primary outcome was change in BIS and EMG values before and after administration of neuromuscular blockade reversal agents (between train-of-four [TOF] count 1-2 and TOF ratio 0.9). The change in BIS and EMG values before and after administration of neuromuscular blockade reversal agents were statistically different in each group (BIS: Neostigmine group, P < 0.001; Sugammadex group, P < 0.001; Pyridostigmine group, P = 0.001; EMG: Neostigmine group, P = 0.001; Sugammadex group, P < 0.001; Pyridostigmine group, P = 0.001; respectively). The BIS and EMG values had a positive correlation (P < 0.001). Our results demonstrate that the EMG and BIS values have increased after neuromuscular blockade reversal under desflurane anesthesia regardless of the type of neuromuscular blockade reversal agent. BIS should be applied carefully to measure of depth of anesthesia after neuromuscular blockade reversal.

The effects of ropivacaine 0.0625% and levobupivacaine 0.0625% on uterine and abdominal muscle electromyographic activity during the second stage of labor.

BACKGROUND: This study investigated the effect of ropivacaine on uterine and abdominal muscle electromyographic activity during the second stage of labor. METHODS: A total of 161 patients, including 48 patients receiving 0.0625% ropivacaine for patient-controlled epidural analgesia (PCEA), 64 patients receiving 0.0625% levobupivacaine for PCEA, and 49 patients with no PCEA completed the study. Uterine and abdominal muscle electromyographic activity was continuously recorded from the abdominal surface during the second stage of labor. Maternal demographic and clinical characteristics, maternal and neonatal outcomes, and various electromyographic parameters were recorded. RESULTS: Second stage of labor was significantly prolonged (P=0.007) for levobupivacaine compared to ropivacaine or no PCEA. The root-mean-square and duration of uterine muscle electromyographic activity was significantly lower for levobupivacaine or ropivacaine compared to no PCEA. The root-mean-square and power of abdominal muscle electromyographic activity was significantly lower for levobupivacaine compared to ropivacaine or no PCEA; the peak frequency of abdominal muscle electromyographic activity was significantly higher for ropivacaine. Visual analogue scale pain scores in patients in the levobupivacaine group or ropivacaine group decreased significantly over time compared to patients in the no PCEA group. CONCLUSIONS: In conclusion 0.0625% ropivacaine does not suppress abdominal muscle electromyographic activity during the second stage of labor. Maternal and neonatal outcomes were similar in patients receiving ropivacaine or no PCEA.

Retinal supplementation augments optogenetic stimulation efficacy in vivo.

OBJECTIVE: Over the last two decades, optical control of neuronal activity in the central nervous system has seen rapid development, demonstrating the utility of optogenetics as both an experimental and therapeutic tool. Conversely, applications of optogenetics in the peripheral nervous system have been relatively constrained by the challenges of temporally variable opsin expression, light penetration and immune attack of non-native opsins. Whilst opsin expression can be increased significantly through high-concentration viral induction, subsequent attack by the immune system causes temporal decay and high variability in electrophysiological response. APPROACH: In this study, we present a method to circumvent the aforementioned challenges by locally supplementing all-trans-retinal (ATR) (via a slow release pellet) to increase tissue photosensitivity in transgenic mice expressing channelrhodopsin 2 (ChR2) in nerves. MAIN RESULTS: In mice supplemented with ATR, we demonstrate enhanced electrophysiological activation and fatigue tolerance in response to optical stimulation for six weeks. SIGNIFICANCE: Local supplementation of ATR enables improved optogenetic stimulation efficacy in peripheral nerves. This method enables greater exploration of neurophysiology and development of clinically-viable optogenetic treatments in the peripheral nervous system.

Effect of local anesthetic volume (20 mL vs 30 mL ropivacaine) on electromyography of the diaphragm and pulmonary function after ultrasound-guided supraclavicular brachial plexus block: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Diaphragmatic paralysis following supraclavicular brachial plexus block (SCBPB) is ascribed to phrenic nerve palsy. This study investigated the effect of 2 volumes of 0.375% ropivacaine on efficacy of block as a surgical anesthetic and as an analgesic and examined diaphragm compound muscle action potentials (CMAPs) and pulmonary function before and after SCBPB. METHODS: Eighty patients scheduled for removal of hardware for internal fixation after healing of an upper limb fracture distal to the shoulder were randomized to receive ultrasound-guided SCBPC for surgical anesthesia with 20 mL (Group A) or 30 mL (Group B) 0.375% ropivacaine. The latency and amplitude of diaphragm CMAPs and forced vital capacity (FVC), FVC% predicted, and forced expiratory volume in 1 s (FEV1) were measured before and 30 min after SCBPB. RESULTS: Block success as primary anesthetic in addition to analgesia was 81% in Group A and 91% in Group B. There were no obvious differences in the effectiveness of analgesia between the two groups. The mean time to onset of motor block was significantly longer in Group A (8.1±2.7 min) than in Group B (5.4 ± 2.8 min; p<0.05). The mean amplitude of the diaphragm CMAP was significantly lower in Group B than in Group A (p=0.03). The changes in FVC (Group A, - 8.1% vs Group B, -16.5%), FVC% (Group A, -8.0% vs Group B, -17.1%), and FEV1 (Group A, -9.5% vs Group B, -15.2%) from pre-SCBPB to post-SCBPB were significantly less in Group A than in Group B (all p=0.03). CONCLUSIONS: The incidence rates of phrenic nerve palsy and diaphragm paralysis were reduced, and lung function was less impaired in patients who received 20 mL vs 30 mL of 0.375% ropivacaine without any differences in block success. Selecting a lower volume of anesthetic for nerve block may be especially beneficial in obese patients or patients with cardiopulmonary disease. TRIAL REGISTRATION NUMBER: ChiCTR-IND-17012166.

Effects of antiepileptic drugs on cortical excitability in humans: A TMS-EMG and TMS-EEG study.

Brain responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) are emergent noninvasive markers of neuronal excitability and effective connectivity in humans. However, the underlying physiology of these TMS-evoked EEG potentials (TEPs) is still heavily underexplored, impeding a broad application of TEPs to study pathology in neuropsychiatric disorders. Here we tested the effects of a single oral dose of three antiepileptic drugs with specific modes of action (carbamazepine, a voltage-gated sodium channel (VGSC) blocker; brivaracetam, a ligand to the presynaptic vesicle protein VSA2; tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor) on TEP amplitudes in 15 healthy adults in a double-blinded randomized placebo-controlled crossover design. We found that carbamazepine decreased the P25 and P180 TEP components, and brivaracetam the N100 amplitude in the nonstimulated hemisphere, while tiagabine had no effect. Findings corroborate the view that the P25 represents axonal excitability of the corticospinal system, the N100 in the nonstimulated hemisphere propagated activity suppressed by inhibition of presynaptic neurotransmitter release, and the P180 late activity particularly sensitive to VGSC blockade. Pharmaco-physiological characterization of TEPs will facilitate utilization of TMS-EEG in neuropsychiatric disorders with altered excitability and/or network connectivity.

Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep.

STUDY OBJECTIVES: A major challenge in treating insomnia is to find effective medicines with fewer side effects. Activation of G-protein-gated inward rectifying K+ channels (GIRKs) by GABAB agonists baclofen or γ-hydroxybutyric acid (GHB) promotes nonrapid eye movement (NREM) sleep and consolidates sleep. However, baclofen has poor brain penetration, GHB possesses abuse liability, and in rodents both drugs cause spike-wave discharges (SWDs), an absence seizure activity. We tested the hypothesis that direct GIRK activation promotes sleep without inducing SWD using ML297, a potent and selective GIRK activator. METHODS: Whole-cell patch-clamp recordings from hypocretin/orexin or hippocampal neurons in mouse brain slices were made to study neuronal excitability and synaptic activity; spontaneous activity, locomotion, contextual and tone-conditioned memory, and novel object recognition were assessed. Electroencephalogram/electromyogram (EEG/EMG) recordings were used to study GIRK modulation of sleep. RESULTS: ML297, like baclofen, caused membrane hyperpolarization, decreased input resistance, and blockade of spontaneous action potentials. Unlike baclofen, ML297 (5-10 µM) did not cause significant depression of postsynaptic excitatory and inhibitory currents (EPSCs-IPSCs), indicating preferential postsynaptic inhibition. ML297 (30 mg/kg, i.p.) inhibited wake activity and locomotion, and preferentially increased NREM sleep without altering EEG delta power, REM sleep, inducing SWDs, or impairing conditioned memory and novel object recognition. CONCLUSIONS: This study finds that direct activation of neuronal GIRK channels modulates postsynaptic membrane excitability and prolongs NREM sleep without changing sleep intensity, inducing SWDs, or impairing memory in rodents. These results suggest that direct GIRK activation with a selective compound may present an innovative approach for the treatment of chronic insomnia.

Toxic doses of caffeine are needed to increase skeletal muscle contractility.

Discrepant results have been reported regarding an intramuscular mechanism underlying the ergogenic effect of caffeine on neuromuscular function in humans. Here, we reevaluated the effect of caffeine on muscular force production in humans and combined this with measurements of the caffeine dose-response relationship on force and cytosolic free [Ca2+] ([Ca2+]i) in isolated mouse muscle fibers. Twenty-one healthy and physically active men (29 ± 9 yr, 178 ± 6 cm, 73 ± 10 kg, mean ± SD) took part in the present study. Nine participants were involved in two experimental sessions during which supramaximal single and paired electrical stimulations (at 10 and 100 Hz) were applied to the femoral nerve to record evoked forces. Evoked forces were recorded before and 1 h after ingestion of 1) 6 mg caffeine/kg body mass or 2) placebo. Caffeine plasma concentration was measured in 12 participants. In addition, submaximal tetanic force and [Ca2+]i were measured in single mouse flexor digitorum brevis (FDB) muscle fibers exposed to 100 nM up to 5 mM caffeine. Six milligrams of caffeine per kilogram body mass (plasma concentration ~40 µM) did not increase electrically evoked forces in humans. In superfused FDB single fibers, millimolar caffeine concentrations (i.e., 15- to 35-fold above usual concentrations observed in humans) were required to increase tetanic force and [Ca2+]i. Our results suggest that toxic doses of caffeine are required to increase muscle contractility, questioning the purported intramuscular ergogenic effect of caffeine in humans.

Effect of a lateral infraclavicular brachial plexus block on the axillary and suprascapular nerves as determined by electromyography - a cohort study.

We aimed to examine to what extent a lateral infraclavicular brachial plexus block affected the axillary and the suprascapular nerve. We included patients undergoing hand surgery anaesthetised with a lateral infraclavicular brachial plexus block. Our primary outcome was the relative change in surface electromyography during maximum voluntary isometric contraction of the medial deltoid muscle (axillary nerve) and the infraspinatus muscle (suprascapular nerve) from baseline to 30 min after the block procedure. A reduction in electromyography of > 50% defined a successful block. The impact of the block on the shoulder nerves was compared with the surgical target nerves of the arm and hand (musculocutaneous, radial, median and ulnar nerves). Twenty patients were included. The medians of the relative changes in the surface electromyography were significantly reduced (both p < 0.001) with 92% for the deltoid muscle and 30% for the infraspinatus muscle, respectively. In total, 18 out of 20 patients had reductions > 50% for the deltoid muscle, which was significantly different from the infraspinatus muscle, where the proportion was 5 out of 20 (p < 0.001). The medians of the relative reductions in electromyography for the arm and hand muscles were 90-96%, similar to the effect on the deltoid muscle. Our results suggest that a lateral infraclavicular block provides block of the axillary nerve comparable to the block of the surgical target nerves. The suprascapular nerve is blocked to a lesser degree. Combining a lateral infraclavicular brachial plexus block with a selective suprascapular block for shoulder surgery warrants further studies.

Local anesthetic effect of docosahexaenoic acid on the nociceptive jaw-opening reflex in rats.

Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1-5 x threshold). At 3 x threshold, local administration of DHA (0.1, 10 and 25 mM) dose-dependently inhibited the dEMG response, and lasted 40 min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10 min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25 mM) was almost equal to the local anesthetic, 1% lidocaine (37 mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception.

REV-ERBß is required to maintain normal wakefulness and the wake-inducing effect of dual REV-ERB agonist SR9009.

Circadian signaling regulates and synchronizes physiological and behavioral processes, such as feeding, metabolism, and sleep cycles. The endogenous molecular machinery that regulates circadian activities is located in the suprachiasmatic nucleus of the hypothalamus. The REV-ERBs are transcription factors that play key roles in the regulation of the circadian clock and metabolism. Using pharmacological methods, we recently demonstrated the involvement of the REV-ERBs in sleep architecture. Another group reported a delayed response to sleep deprivation and altered sleep cycles in REV-ERBα null mice, indicating a role of REV-ERBα in sleep. Given that REV-ERBß is structurally and functionally similar to REV-ERBα, we investigated the role of REV-ERBß in sleep and wakefulness by assessing electroencephalographic recordings in REV-ERBß deficient mice and the mechanism underlying effects of loss of REV-ERBß on sleep. Our data suggest that REV-ERBß is involved in the maintenance of wakefulness during the activity period. In addition, REV-ERBß-deficient mice administered with dual REV-ERB agonist SR9009, failed to show drug-induced wake increase. Finally, the expression of a number of genes known to mediate sleep and wakefulness were altered in REV-ERBß null mice.

Spectral EMG Changes in Cervical Dystonia Patients and the Influence of Botulinum Toxin Treatment.

Botulinum toxin (BoNT) injections in the dystonic muscles is the preferred treatment for Cervical Dystonia (CD), but the proper identification of the dystonic muscles remains a challenge. Previous studies showed decreased 8-14 Hz autospectral power in the electromyography (EMG) of splenius muscles in CD patients. Cumulative distribution functions (CDF's) of dystonic muscles showed increased CDF10 values, representing increased autospectral powers between 3 and 10 Hz, relative to power between 3 and 32 Hz. In this study, we evaluated both methods and investigated the effects of botulinum toxin. Intramuscular EMG recordings were obtained from the splenius, semispinalis, and sternocleidomastoid muscles during standardized isometric tasks in 4 BoNT-naïve CD patients, 12 BoNT-treated patients, and 8 healthy controls. BoNT-treated patients were measured 4-7 weeks after their last BoNT injections and again after 11-15 weeks. We found significantly decreased 8-14 Hz autospectral power in splenius muscles, but not in the semispinalis and sternocleidomastoid muscles of CD patients when compared to healthy controls. CDF10 analysis was superior in demonstrating subtle autospectral changes, and showed increased CDF10 values in all studied muscles of CD patients. These results did not change significantly after BoNT injections. Further studies are needed to investigate the origin of these autospectral changes in dystonia patients, and to assess their potential in muscle selection for BoNT treatment.