Ultrasound-guided transversalis fascia plane block versus transmuscular quadratus lumborum block for post-operative analgesia in inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is one of the most commonly performed surgical procedures. Regional blocks might provide excellent analgesia and reduce complications in the postoperative period. We aimed to compare the postoperative analgesic effect of the ultrasound-guided transversalis fascia (TF) plane block versus the transmuscular quadratus lumborum (QL) block in patients undergoing unilateral inguinal hernia repair. METHODS: Fifty patients enrolled in this comparative study and were randomly assigned into two equal groups. One group received an ultrasound-guided QL block. In comparison, the other group received an ultrasound-guided TF plane block. The primary outcome was the patient-assessed resting, and movement-induced pain on the numeric pain rating scale (NRS) measured at 30 minutes postoperatively. Secondary outcomes included the percentage of patients receiving rescue analgesia in the first postoperative day, ease of performance of the technique, and incidence of adverse effects. RESULTS: There were no statistically significant differences in NRS at rest and with movement between the groups over the first 24 hours postoperatively. The proportion of patients that received postoperative rescue analgesics during the first 30 minutes postoperatively was 4% (n = 1) in the QL group compared to 12% (n = 3) in the TF group. However, the mean performance time of the TF block was shorter than that of the QL block, and the performance of the TF block appeared easier technically. CONCLUSIONS: The ultrasound-guided TF plane block could be as effective as the QL block in lowering pain scores and decreasing opioid consumption following non-recurrent inguinal herniorrhaphy.

The Success Rate of Ultrasound-Guided Sacroiliac Joint Steroid Injections in Sacroiliitis: Are We Getting Better?

BACKGROUND: The sacroiliac joint is one of the most common sources of low back pain; however, it is difficult to place the needle accurately inside the joint space without image guidance. Improvement of ultrasound technology may lead to a high success rate for intra-articular drug deposition. OBJECTIVE: Assessment of the success rate of ultrasound-guided intra-articular sacroiliac joint injection. DESIGN: Prospective observational study. METHODOLOGY: Ultrasound-guided injections were performed on 34 patients suffering from sacroiliitis. After injection of the drug solution and withdrawal of the needle, an anteroposterior fluoroscopy image was obtained and recorded for the injected joint to detect whether it was predominantly intra-articular or peri-articular. Clinical outcome using a numeric pain rating scale as well as limitation of physical functioning measured by the Oswestry Disability Index (ODI) were determined. RESULTS: Thirty-three injections (84.6%) were intra-articular, while 6 injections (15.4%) were peri-articular, as confirmed by fluoroscopy, with no statistical difference regarding clinical outcome between them. The baseline mean pain score decreased from 7.21 to 1.92 1 month after injection, and the mean ODI scores improved from 61.41% to 17.13%. Intervention was well tolerated, and 91.2% of patients were satisfied or mostly satisfied. CONCLUSION: Ultrasonography provides a high success rate of intra-articular sacroiliac joint injection as confirmed by fluoroscopy. No significant difference in clinical outcome between intra-articular and peri-articular injection was found.

Repeated anodal trans-spinal direct current stimulation results in long-term reduction of spasticity in mice with spinal cord injury.

KEY POINTS: Spasticity is a disorder of muscle tone that is associated with lesions of the motor system. This condition involves an overactive spinal reflex loop that resists the passive lengthening of muscles. Previously, we established that application of anodal trans-spinal direct current stimulation (a-tsDCS) for short periods of time to anaesthetized mice sustaining a spinal cord injury leads to an instantaneous reduction of spasticity. However, the long-term effects of repeated a-tsDCS and its mechanism of action remained unknown. In the present study, a-tsDCS was performed for 7 days and this was found to cause long-term reduction in spasticity, increased rate-dependent depression in spinal reflexes, and improved ground and skill locomotion. Pharmacological, molecular and cellular evidence further suggest that a novel mechanism involving Na-K-Cl cotransporter isoform 1 mediates the observed long-term effects of repeated a-tsDCS. ABSTRACT: Spasticity can cause pain, fatigue and sleep disturbances; restrict daily activities such as walking, sitting and bathing; and complicate rehabilitation efforts. Thus, spasticity negatively influences an individual's quality of life and novel therapeutic interventions are needed. We previously demonstrated in anaesthetized mice that a short period of trans-spinal subthreshold direct current stimulation (tsDCS) reduces spasticity. In the present study, the long-term effects of repeated tsDCS to attenuate abnormal muscle tone in awake female mice with spinal cord injuries were investigated. A motorized system was used to test velocity-dependent ankle resistance and associated electromyographical activity. Analysis of ground and skill locomotion was also performed, with electrophysiological, molecular and cellular studies being conducted to reveal a potential underlying mechanism of action. A 4 week reduction in spasticity was associated with an increase in rate-dependent depression of spinal reflexes, and ground and skill locomotion were improved following 7 days of anodal-tsDCS (a-tsDCS). Secondary molecular, cellular and pharmacological experiments further demonstrated that the expression of K-Cl co-transporter isoform 2 (KCC2) was not changed in animals with spasticity. However, Na-K-Cl cotransporter isoform 1 (NKCC1) was significantly up-regulated in mice that exhibited spasticity. When mice were treated with a-tsDCS, down regulation of NKCC1 was detected, and this level did not significantly differ from that in the non-injured control mice. Thus, long lasting reduction of spasticity by a-tsDCS via downregulation of NKCC1 may constitute a novel therapy for spasticity following spinal cord injury.

Novel Speed-Controlled Automated Ladder Walking Device Reveals Walking Speed as a Critical Determinant of Skilled Locomotion after a Spinal Cord Injury in Adult Rats.

The horizontal ladder task is an established method to assess skilled locomotor recovery after neurological dysfunction. Walking speed is often used as a standardized measure in locomotor assessment of overground walking in human and pre-clinical studies, but the assessment of walking speed is typically ignored during skilled locomotor tasks. Ample empirical evidence indicates that walking speeds on the horizontal ladder are largely non-uniform after central nervous system trauma, suggesting that it could pose a potential source of variability in assessing motor deficits. Here, we investigate whether walking speed influences the assessment of motor recovery during skilled walking after a spinal cord injury (SCI). We hypothesized that if rats walk at imposed walking speeds, motor deficits and recovery after an SCI will be more reliably assessed than when not controlling walking speeds. To address this, we developed a novel speed-controlled Automated Device for the Assessment and Training of Skilled locomotion (ADATS) as a surrogate device to the horizontal ladder. The ADATS allows testing at user-defined speeds, thereby forcing the rats to step consistently. Our results demonstrate that: 1) the ability to walk (or not) at one or multiple speeds on the ADATS serves as a gross measure of motor dysfunction/recovery after a spinal cord injury and 2) skilled motor deficits are more readily detected at lower than higher walking speeds. We conclude that walking speed is an important factor in the analyses of skilled locomotion and testing at multiple speeds is useful in accurately measuring recovery after neurotrauma in rats.

Non-invasive treatment of patients with upper extremity spasticity following stroke using paired trans-spinal and peripheral direct current stimulation.

BACKGROUND: Muscle spasticity is a common impediment to motor recovery in patients with chronic stroke. Standard-of-care treatments such as botulinum toxin injections can temporarily relieve muscle stiffness and pain associated with spasticity, but often at the expense of increased muscle weakness. Recent preclinical investigations of a non-invasive treatment that pairs trans-spinal direct current stimulation and peripheral nerve direct current stimulation (tsDCS+pDCS) provided promising data for a novel approach based on bioelectronic medicine for the treatment of patients with post-stroke spasticity. METHODS: Twenty-six patients with upper limb hemiparesis and wrist spasticity at least 6 months after their initial stroke participated in this single-blind crossover design study to test whether tsDCS+pDCS reduces chronic upper-extremity spasticity. Subjects received five consecutive daily sessions (20 min of stimulation or sham) of anodal tsDCS+pDCS, separated by a one-week washout period. The sham condition always preceded the active condition. Clinical and objective measures of spasticity and motor function were collected before and after each condition, and for five weeks after the completion of the active intervention. RESULTS: Subjects treated with active tsDCS+pDCS demonstrated significant reductions in both Modified Tardieu Scale scores (summed across the upper limb, P < 0.05), and in objective torque measures (Nm) of the spastic catch response at the wrist flexor (P < 0.05), compared to the sham condition. Motor function also improved significantly (measured by the Fugl-Meyer and Wolf Motor Function Test; P < 0.05 for both tests) after active treatment. CONCLUSIONS: tsDCS+pDCS intervention alone significantly reduced upper limb spasticity in participants with stroke. Decreased spasticity was persistent for five weeks after treatment, and was accompanied by improved motor function even though patients were unsupervised and there was no prescribed activity or training during that interval. TRIAL REGISTRATION: NCT03080454, March 15, 2017.

Real-time ultrasound-guided retrobulbar block vs blind technique for cataract surgery (pilot study).

BACKGROUND: Retrobulbar regional eye block aims to ensure eye globe akinesia and anesthesia during ophthalmic surgery, and despite the rarity of occurrence of complications due to the blind needle passage while performing either peribulbar or retrobulbar block, some of them are serious and may be life threatening. AIM: The aim of this study was to estimate the accuracy and safety of real-time ultrasound-guided retrobulbar regional anesthesia in comparison with the blind technique for cataract surgery. DESIGN: This was a prospective randomized controlled trial. METHODOLOGY: A total of 30 patients who met the inclusion criteria were registered in our research and were divided into two groups: 15 patients received real-time ultrasound-guided retrobulbar block compared to 15 patients who received the block using the blind technique. RESULTS: One patient out of the 30 was excluded from the analysis, and no statistically significant differences were observed between the two groups regarding the onset of akinesia, numeric pain rating scores, rate of complications, and degree of patient and physician satisfaction. CONCLUSION: There were no statistically significant difference between real-time ultrasound-guided and blind retrobulbar regional eye blocks concerning the onset of action, total volume of injected local anesthetic solution, supplemental injection required, pain scores, and degree of patient satisfaction.

Comparison of 3 Approaches to Percutaneous Epidural Adhesiolysis and Neuroplasty in Post Lumbar Surgery Syndrome.

BACKGROUND: Percutaneous epidural adhesiolysis and neuroplasty (PEAN) has been proven to be safe and effective in treating different spine pathologies, in particular post lumbar surgery syndrome (PLSS). OBJECTIVES: The purpose of this study was to compare the efficacy and complication rates of the 3 different PEAN anatomical approaches (caudal, S1 foraminal, and L5-S1 transforaminal) used to treat PLSS. STUDY DESIGN: This study used a case control, blind study. SETTING: The research took place at the pain clinic and interventional pain practice room at Asyut University Hospital, Assiut, Egypt. METHODS: Sixty consecutive PLSS patients were recruited and randomized into 3 groups (caudal, S1 foraminal, and L5-S1 transforaminal) before receiving adhesiolysis and neuroplasty. All patients underwent nerve conduction studies and magnetic resonance imaging (MRI). Pain severity levels were assessed and measured using the Oswestry Disability Questionnaire (OSW) and the Visual Analog Scale (VAS). Patient satisfaction was evaluated using a Likert scale. The first assessment was performed prior to the procedure to determine the patients' baseline levels of pain severity. Follow-up assessments were performed 1-, 3-, and 6-months after the procedure. RESULTS: Results of the group pairwise analysis indicated that, relative to baseline, there were significant decreases in pain relief scores (VAS and OWS) and functional assessment expressed by patients' satisfaction across all time intervals and in all 3 groups (P < 0.01). Conversely, a between group analysis revealed that VAS, OWS, and patient satisfaction scores were comparable across the 3 groups at all time intervals (P > 0.05). There were no differences in rates of complications between the 3 different groups. LIMITATIONS: Our study was limited by the low number of patients and the short duration (6 months) of follow-up. CONCLUSION: The 3 anatomical approaches (caudal, S1 foraminal, and L5-S1 transforaminal) result in the same outcome with regard to pain relief and complication rate. KEY WORDS: Post lumber surgery syndrome, post laminectomy back pain, percutaneous adhesiolysis, Racz catheter, percutaneous neuroplasty.

Effects of cathodal trans-spinal direct current stimulation on lower urinary tract function in normal and spinal cord injury mice with overactive bladder.

OBJECTIVE: Lower urinary tract (LUT) dysfunction is a monumental problem affecting quality of life following neurotrauma, such as spinal cord injury (SCI). Proper function of the bladder and its associated structures depends on coordinated activity of the neuronal circuitry in the spinal cord and brain. Disconnection between the spinal and brain centers controlling the LUT causes fundamental changes in the mechanisms involved in the micturition and storage reflexes. We investigated the effects of cathodal trans-spinal direct current stimulation (c-tsDCS) of the lumbosacral spine on bladder and external urinary sphincter (EUS) functions. APPROACH: We used cystometry and electromyography (EMG), in mice with and without SCI. MAIN RESULTS: c-tsDCS caused initiation of the micturition reflex in urethane-anesthetized normal mice with depressed micturition reflexes. This effect was associated with normalized EUS-EMG activity. Moreover, in urethane-anesthetized normal mice with expressed micturition reflexes, c-tsDCS increased the firing frequency, amplitude, and duration of EUS-EMG activity. These effects were associated with increased maximum intravesical pressure (P max) and intercontraction interval (ICI). In conscious normal animals, c-tsDCS caused significant increases in P max, ICI, threshold pressure (P thres), baseline pressure (P base), and number and amplitude of non-voiding contractions (NVCnumb and P im, respectively). In conscious mice with severe contusive SCI and overactive bladder, c-tsDCS increased P max, ICI, and P thres, but decreased P base, NVCnumb, and P im. c-tsDCS reduced the detrusor-overactivity/cystometry ratio, which is a measure of bladder overactivity associated with renal deterioration. SIGNIFICANCE: These results indicate that c-tsDCS induces robust modulation of the lumbosacral spinal-cord circuitry that controls the LUT.

Transspinal direct current stimulation modulates migration and proliferation of adult newly born spinal cells in mice.

Direct current electrical fields have been shown to be a major factor in the regulation of cell proliferation, differentiation, migration, and survival, as well as in the maturation of dividing cells during development. During adulthood, spinal cord cells are continuously produced in both animals and humans, and they hold great potential for neural restoration following spinal cord injury. While the effects of direct current electrical fields on adult-born spinal cells cultured ex vivo have recently been reported, the effects of direct current electrical fields on adult-born spinal cells in vivo have not been characterized. Here, we provide convincing findings that a therapeutic form of transspinal direct current stimulation (tsDCS) affects the migration and proliferation of adult-born spinal cells in mice. Specifically, cathodal tsDCS attracted the adult-born spinal cells, while anodal tsDCS repulsed them. In addition, both tsDCS polarities caused a significant increase in cell number. Regarding the potential mechanisms involved, both cathodal and anodal tsDCS caused significant increases in expression of brain-derived neurotrophic factor, while expression of nerve growth factor increased and decreased, respectively. In the spinal cord, both anodal and cathodal tsDCS increased blood flow. Since blood flow and angiogenesis are associated with the proliferation of neural stem cells, increased blood flow may represent a major factor in the modulation of newly born spinal cells by tsDCS. Consequently, we propose that the method and novel findings presented in the current study have the potential to facilitate cellular, molecular, and/or bioengineering strategies to repair injured spinal cords.NEW & NOTEWORTHY Our results indicate that transspinal direct current stimulation (tsDCS) affects the migratory pattern and proliferation of adult newly born spinal cells, a cell population which has been implicated in learning and memory. In addition, our results suggest a potential mechanism of action regarding the functional effects of applying direct current. Thus tsDCS may represent a novel method by which to manipulate the migration and cell number of adult newly born cells and restore functions following brain or spinal cord injury.

Modulation of gamma and alpha spinal motor neurons activity by trans-spinal direct current stimulation: effects on reflexive actions and locomotor activity.

Spontaneous and evoked spinal activities interact to set the characteristics of emergent motor responses. Gamma motor neurons have feedforward and feedback functions in motor control, which are crucial for transforming motor commands into action. Meanwhile, the intrinsic excitability and functional connectivity of alpha motor neurons determine the accuracy of actions. In this study, we investigated the effects of trans-spinal direct current stimulation (tsDCS) on spontaneous and cortically evoked activity of well-isolated single units of gamma and alpha motor neurons in mice. We also investigated the effects of tsDCS on reflexive and locomotor actions. In general, motor neurons showed increased responses to cathodal tsDCS (c-tsDCS) and decreased responses to anodal tsDCS (a-tsDCS). These effects were observed for cortically evoked discharges and spontaneous firing rates of gamma motor neurons, cortically evoked discharges of larger alpha motor neurons, and spontaneous firing rates of smaller alpha motor neurons. An exception was that spontaneous firing rates of larger alpha motor neurons showed the opposite pattern of reduction by c-tsDCS and increase by a-tsDCS. Reflexive and voluntary behavior were also increased by c-tsDCS and reduced by a-tsDCS. Specifically, the amplitude and duration of crossed and tail pinch reflexes in decerebrate animals and the quality of ground and treadmill walking patterns in healthy awake animals showed this pattern. These polarity-specific changes in behavior could be attributed to polarity-mediated modulation of alpha and gamma motor neuron activity and spinal circuitry. The results reveal an important principle: effects of tsDCS on spinal motor neurons depend on current polarity and cell size.

Direct Current-Induced Calcium Trafficking in Different Neuronal Preparations.

The influence of direct current (DC) stimulation on radioactive calcium trafficking in sciatic nerve in vivo and in vitro, spinal cord, and synaptosomes was investigated. The exposure to DC enhanced calcium redistribution in all of these preparations. The effect was dependent on the strength of the stimulation and extended beyond the phase of exposure to DC. The DC-induced increase in calcium sequestration by synaptosomes was significantly reduced by cobalt and rupture of synaptosomes by osmotic shock. Although both anodal and cathodal currents were effective, the experiments with two electrodes of different areas revealed that cathodal stimulation exerted stronger effect. The exposure to DC induced not only relocation but also redistribution of calcium within segments of the sciatic nerve. Enzymatic removal of sialic acid by preincubation of synaptosomes with neuroaminidase, or carrying out the experiments in sodium-free environment, amplified DC-induced calcium accumulation.

Pulsed magnetic stimulation modifies amplitude of action potentials in vitro via ionic channels-dependent mechanism.

This paper investigates the influence of pulsed magnetic fields (PMFs) on amplitude of evoked, compound action potential (CAP) recorded from the segments of sciatic nerve in vitro. PMFs were applied for 30 min at frequency of 0.16 Hz and intensity of 15 mT. In confirmation of our previous reports, PMF exposure enhanced amplitude of CAPs. The effect persisted beyond PMF activation period. As expected, CAP amplitude was attenuated by antagonists of sodium channel, lidocaine, and tetrodotoxin. Depression of the potential by sodium channels antagonists was reversed by subsequent exposure to PMFs. The effect of elevated potassium concentration and veratridine on the action potential was modified by exposure to PMFs as well. Neither inhibitors of protein kinase C and protein kinase A, nor known free radicals scavengers had any effects on PMF action. Possible mechanisms of PMF action are discussed.

Trans-spinal direct current stimulation modifies spinal cord excitability through synaptic and axonal mechanisms.

The spinal cord is extremely complex. Therefore, trans-spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal-tsDCS (c-tsDCS), but reduced during anodal-tsDCS (a-tsDCS). After-effects were dependent on the frequency of the test stimulation. c-tsDCS-reduced responses evoked by low-frequency (0.5 Hz) test stimulation and increased responses evoked by high-frequency (400 Hz) test stimulation. a-tsDCS had opposite effects. During and after c-tsDCS, excitability of the lateral funiculus tract (LFT) and dorsal root fibers was increased. However, a-tsDCS caused a complex response, reducing the excitability of LFT and increasing dorsal root fiber responses. Local DC application on the sciatic nerve showed that the effects of DC on axonal excitability were dependent on polarity, duration of stimulation, temporal profile (during vs. after stimulation), orientation of the current direction relative to the axon and relative to the direction of action potential propagation, distance from the DC electrode, and the local environment of the nervous tissue. Collectively, these results indicate that synaptic as well as axonal mechanisms might play a role in tsDCS-induced effects. Therefore, this study identified many factors that should be considered in interpreting results of DCS and in designing tsDCS-based interventions.

Trans-spinal direct current stimulation alters muscle tone in mice with and without spinal cord injury with spasticity.

Muscle tone abnormalities are associated with many CNS pathologies and severely limit recovery of motor control. Muscle tone depends on the level of excitability of spinal motoneurons and interneurons. The present study investigated the following hypotheses: (1) direct current flowing from spinal cord to sciatic nerve [spinal-to-sciatic direct current stimulation (DCS)] would inhibit spinal motor neurons and interneurons, hence reducing muscle tone; and (2) direct current flowing in the opposite direction (sciatic-to-spinal DCS) would excite spinal motor neurons and interneurons, hence increasing muscle tone. Current intensity was biased to be ~170 times greater at the spinal column than at the sciatic nerve. The results showed marked effects of DCS on muscle tone. In controls and mice with spinal cord injuries with spasticity, spinal-to-sciatic DCS reduced transit and steady stretch-induced nerve and muscle responses. Sciatic-to-spinal DCS caused opposite effects. These findings provide the first direct evidence that trans-spinal DCS can alter muscle tone and suggest that this approach could be used to reduce both hypotonia and hypertonia.

Effects of cathodal trans-spinal direct current stimulation on mouse spinal network and complex multijoint movements.

Cathodal trans-spinal direct current (c-tsDC) stimulation is a powerful technique to modulate spinal excitability. However, the manner in which c-tsDC stimulation modulates cortically evoked simple single-joint and complex multijoint movements is unknown. To address this issue, anesthetized mice were suspended with the hindlimb allowed to move freely in space. Simple and complex multijoint movements were elicited with short and prolonged trains of electrical stimulation, respectively, delivered to the area of primary motor cortex representing the hindlimb. In addition, spinal cord burst generators are known to be involved in a variety of motor activities, including locomotion, postural control, and voluntary movements. Therefore, to shed light into the mechanisms underlying movements modulated by c-tsDC stimulation, spinal circuit activity was induced using GABA and glycine receptor blockers, which produced three rates of spinal bursting activity: fast, intermediate, and slow. Characteristics of bursting activity were assessed during c-tsDC stimulation. During c-tsDC stimulation, significant increases were observed in (1) ankle dorsiflexion amplitude and speed; (2) ankle plantarflexion amplitude, speed, and duration; and (3) complex multijoint movement amplitude, speed, and duration. However, complex multijoint movement tracing showed that c-tsDC did not change the form of movements. In addition, spinal bursting activity was significantly modulated during c-tsDC stimulation: (1) fast bursting activity showed increased rate, amplitude, and duration; (2) intermediate bursting activity showed increased rate and duration, but decreased amplitude; and (3) slow bursting activity showed increased rate, but decreased duration and amplitude. These results suggest that c-tsDC stimulation amplifies cortically evoked movements through spinal mechanisms.

The effects of 15 Hz trans-spinal magnetic stimulation on locomotor control in mice with chronic contusive spinal cord injury.

The effects of repetitive trans-spinal magnetic stimulation (rTSMS), combined with acrobatic exercise on functional locomotor recovery in chronic spinal-contused mice were tested. The exposure to magnetic stimulation was initiated 3 weeks after injury, when the animals entered chronic stage. The rTSMS was applied for a total of 4 weeks over a 9-week duration trial. Seventeen mice with the spinal cord contusion injured at level T13 were separated into two groups. While one group consisting of 10 animals was exposed to rTSMS (15 Hz), the other seven animals served as controls. Functional recovery measured with Basso mouse scale and horizontal ladder scale showed significantly better functional recovery in rTSMS-treated animals. The progress in recovery continued even after cessation of magnetic stimulation. In vitro experiments revealed that the release of glutamate analog, radioactive D-aspartate from the segments of the spinal cord exposed to rTSMS was significantly elevated. In conclusion, the exposure to rTSMS, applied to injured spinal cord during chronic post-surgery stage remarkably improves the functional recovery. This recovery may be correlated by magnetically induced elevation in the release of major excitatory neurotransmitter, glutamate from injured tissue.

Electrophysiological characterization of spino-sciatic and cortico-sciatic associative plasticity: modulation by trans-spinal direct current and effects on recovery after spinal cord injury in mice.

Associative stimulation causes enduring changes in the nervous system based on the Hebbian concept of spike-timing-dependent plasticity. The present study aimed to characterize the immediate and long-term electrophysiological effects of associative stimulation at the level of spinal cord and to test how trans-spinal direct current stimulation (tsDC) modulates associative plasticity. The effect of combined associative stimulation and tsDC on locomotor recovery was tested in a unilateral model of spinal cord injury (SCI). Two associative protocols were tested: (1) spino-sciatic associative (SSA) protocol, in which the first stimulus originated from the sciatic nerve and the second from the spinal cord; and (2) cortico-sciatic associative (CSA) protocol, in which the first stimulus originated from the sciatic nerve and the second from the motor cortex. In addition, those two protocols were repeated in combination with cathodal tsDC application. SSA and CSA stimulation produced immediate enhancement of spinal and cortical outputs, respectively, depending on the duration of the interstimulus interval. Repetitive SSA or CSA stimulation produced long-term potentiation of spinal and cortical outputs, respectively. Applying tsDC during SSA or CSA stimulation markedly enhanced their immediate and long-term effects. In behaving mice with unilateral SCI, four consecutive 20 min sessions of CSA + tsDC markedly reduced error rate in a horizontal ladder-walking test. Thus, this form of artificially enhanced associative connection can be translated into a form of motor relearning that does not depend on practice or experience.

A novel intubation technique in bilateral cleft palate pediatric patients: hard gum shield-aided intubation.

BACKGROUND: Cleft palate anesthesia is challenging due to difficult airway. Left paraglossal intubation moves resting point of laryngoscope laterally but associated with narrower laryngoscopic view and possible trauma, and we invented the use of hard gum shield as a bridge over defective palate to facilitate intubation with possible wider window and defective tissue protection. METHODS: Eighty bilateral cleft palate children, ASA physical status I-II aged 9 months to 6 years scheduled for plastic surgery had general anesthesia, were involved in prospective, controlled, randomized study, and were randomly divided by closed envelope method into two groups: group I (40 patients): intubated by hard gum shield-aided intubation and group II (40 patients): intubated by left paraglossal intubation. Both techniques compared as regards (i) intubation time; (ii) Cormack and Lehane score; (iii) need for external laryngeal manipulation; (iv) easiness of intubation: easy, modest, or difficult intubation; and (v) complications: desaturation and failed intubation. RESULTS: Intubation time was shorter in group I (28.47 ± 3.78 vs. 37.63 ± 6.64 s, P = 0.001). Cormack and Lehane score was better in group I (P = 0.003). Need for external laryngeal manipulation was less in group I (P = 0.015). Easiness of intubation was better in group I (P = 0.022). No difference was found in complications between groups. CONCLUSION: Hard gum shield-aided intubation facilitated intubation more than left paraglossal in bilateral cleft palate children with shorter intubation time, better glottic view, easier intubation, less need for laryngeal manipulation than left paraglossal intubation with no difference in complications.

Trans-spinal direct current enhances corticospinal output and stimulation-evoked release of glutamate analog, D-2,3-³H-aspartic acid.

Trans-spinal direct current (tsDC) stimulation is a modulator of spinal excitability and can influence cortically elicited muscle contraction in a polarity-dependent fashion. When combined with low-frequency repetitive cortical stimulation, cathodal tsDC [tsDC(-)] produces a long-term facilitation of cortically elicited muscle actions. We investigated the ability of this combined stimulation paradigm to facilitate cortically elicited muscle actions in spinal cord-injured and noninjured animals. The effect of tsDC-applied alone or in combination with repetitive spinal stimulation (rSS) on the release of the glutamate analog, D-2,3-(3)H-aspartate (D-Asp), from spinal cord preparations in vitro-was also tested. In noninjured animals, tsDC (-2 mA) reproducibly potentiated cortically elicited contractions of contralateral and ipsilateral muscles tested at various levels of baseline muscle contraction forces. Cortically elicited muscle responses in animals with contusive and hemisectioned spinal cord injuries (SCIs) were similarly potentiated. The combined paradigm of stimulation caused long-lasting potentiation of cortically elicited bilateral muscle contraction in injured and noninjured animals. Additional analysis suggests that at higher baseline forces, tsDC(-) application does not increase the rising slope of the muscle contraction but causes repeated firing of the same motor units. Both cathodal and anodal stimulations induced a significant increase of D-Asp release in vitro. The effect of the combined paradigm of stimulation (tsDC and rSS) on the concentration of extracellular D-Asp was polarity dependent. These results indicate that tsDC can powerfully modulate the responsiveness of spinal cord neurons. The results obtained from the in vitro preparation suggest that the changes in neuronal excitability were correlated with an increased concentration of extracellular glutamate. The combined paradigm of stimulation, used in our experiments, could be noninvasively applied to restore motor control in humans with SCI.

Clozapine functions through the prefrontal cortex serotonin 1A receptor to heighten neuronal activity via calmodulin kinase II-NMDA receptor interactions.

Aberrant dopamine release in the prefrontal cortex (PFC) is believed to underlie schizophrenia, but the mechanistic pathway through which a widely used antipsychotic, clozapine (Clz), evokes neurotransmitter-releasing electrical stimulation is unclear. We analyzed Clz-evoked regulation of neuronal activity in the PFC by stimulating axons in layers IV and V and recording the electrical effect in the post-synaptic pyramidal cells of layers II and III. We observed a Clz-evoked increase in population spike (PS), which was mediated by serotonin 1A receptor (5-HT(1A)-R), phospholipase Cß, and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Immunoblotting demonstrated that the Clz-activation of CaMKII was 5-HT(1A)-R-mediated. Intriguingly, the NMDA receptor (NMDA-R) antagonist (±)2-amino-5-phosphonovaleric acid (APV) eliminated the Clz-mediated increase in PS, suggesting that the 5-HT(1A)-R, NMDA-R and CaMKII form a synergistic triad, which boosts excitatory post-synaptic potential (EPSP), thereby enhancing PS. In corroboration, Clz as well as NMDA augmented field EPSP (fEPSP), and WAY100635 (a 5-HT(1A)-R antagonist), APV, and a CaMKII inhibitor eliminated this increase. As previously shown, CaMKII binds to the NMDA-R 2B (NR2B) subunit to become constitutively active, thereby inducing α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor recruitment to the post-synaptic membrane and an increase in fEPSP. Co-immunoprecipitation demonstrated that Clz potentiates interactions among CaMKII, NR2B, and 5-HT(1A)-R, possibly in the membrane rafts of the post-synaptic density (PSD), because pretreatment with methyl-ß-cyclodextrin (MCD), an agent that disrupts rafts, inhibited both co-immunoprecipitation as well as fEPSP. In summary, Clz functions in the PFC by orchestrating a synergism among 5-HT(1A)-R, CaMKII, and NMDA-R, which augments excitability in the PFC neurons of layers II/III.