Determination of the Minimum Infusion Rate of Alfaxalone Combined with Electroacupuncture in Goats

Total intravenous anesthesia (TIVA) is increasingly used in companion animals. The effect of electroacupuncture (EA) on alfaxalone-based TIVA has not been previously reported in goats. Therefore, the objective of this study was to determine the minimum infusion rate (MIR) of alfaxalone required to prevent purposeful movement of the extremities in response to standardized noxious stimulation during its combination with EA in goats. Twelve clinically healthy goats weighing 18.5 ± 2 kg were randomly assigned to two groups (six goats/group). Alfaxalone alone (ALF group) and alfaxalone combined with EA (EA-ALF group). In the EA-ALF, alfaxalone was administered 30 min after EA stimulation. For induction of anesthesia, a bolus of alfaxalone was given at 3 mg/kg IV, and an infusion dose of 9.6 mg/kg/h was initially set for maintenance. The MIR of alfaxalone in both groups was determined by testing for responses to stimulation (clamping on a digit with Vulsellum forceps) at 10-min intervals after induction of anesthesia till the entire period of the experiment. Cardiopulmonary parameters and nociceptive threshold were measured throughout anesthesia. The median alfaxalone MIR was significantly lower in the EA-ALF group than the ALF group [9 (4.8–9.6) and 12 (11.4–18)], respectively; p = 0.0035). In the ALF group, goats anesthetized with MIR showed a significant increase in heart rate and cardiac output (p < 0.0001 and 0.0312, respectively), and decrease in respiratory rate (p < 0.0001), hemoglobin oxygen saturation (p = 0.0081), and rectal temperature (p = 0.0046) compared with those in the EA-ALF. Additionally, goats in the EA-ALF showed a higher nociceptive threshold than those in the ALF group (p < 0.0001). EA provided analgesia, reduced the MIR of alfaxalone-based IV anesthesia and thereby alleviated the adverse cardiorespiratory effects associated with alfaxalone anesthesia in goats.

Altered Brain Functional Network Dynamics in Classic Trigeminal Neuralgia: A Resting-state Functional Magnetic Resonance Imaging Study

Background: Accumulating studies have indicated a wide range of brain alterations in structure and function of Classic trigeminal neuralgia (CTN). Given the dynamic nature of pain experience, the exploration of temporal fluctuations in interregional activity covariance may enhance the understanding of pain process in brain. The present study aimed to characterize the temporal features of functional connectivity (FC) states as well as topological alteration in CTN.Methods: Resting-state fMRI (rs-fMRI) and three-dimensional T1-weighted images were obtained from 41 CTN patients and 43 matched healthy controls (HC). After group independent component analysis, sliding window based dynamic functional network connectivity (dFNC) analysis was applied to investigate specific FC states and related temporal properties. Then the dynamics in whole brain topological organization were estimated by calculating coefficient of variation of graph-theoretical properties. The further correlation analysis were performed between all those measurements and clinical data.Results: Two distinct states were identified, of which the state 2, characterized by complicate coupling between default mode network (DMN) and cognitive control network (CC) and tight connections within DMN, expressed more in CTN patients, presented as increased fractional windows and dwell time. Also, patients switched less frequently between states than HC. Regarding to dynamic topological analysis, disruptions in global graph-theoretical properties (including network efficiency and small-worldness) were observed in patients, coupled with decreased variability in nodal efficiency of anterior cingulate cortex (ACC) in salience network (SN) and thalamus, caudate in subcortical network (SC). The variation of topological properties showed negative correlation with disease duration and attack frequency.Conclusions: The present study indicated disrupted flexibility of brain topological organization under persistent noxious stimulation and further highlighted the important role of “dynamic pain connectome” regions (including DMN/CC/SN) in pathophysiology of CTN from temporal fluctuation aspect. Additionally, the findings provided supplementary evidence for current knowledge about the aberrant cortical-subcortical interaction in pain development.

A Review on Various Topics on the Thermal Grill Illusion

The thermal grill illusion (TGI) is a paradoxical perception of burning heat and pain resulting from the simultaneous application of interlaced warm and cold stimuli to the skin. The TGI is considered a type of chronic centralized pain and has been used to apply nociceptive stimuli without inflicting harm to human participants in the study of pain mechanisms. In addition, the TGI is an interesting phenomenon for researchers, and various topics related to the TGI have been investigated in several studies, which we will review here. According to previous studies, the TGI is generated by supraspinal interactions. To evoke the TGI, cold and warm cutaneous stimuli should be applied within the same dermatome or across dermatomes corresponding to adjacent spinal segments, and a significant difference between cold and warm temperatures is necessary. In addition, due the presence of chronic pain, genetic factors, and sexual differences, the intensity of the TGI can differ. In addition, cold noxious stimulation, topical capsaicin, analgesics, self-touch, and the presence of psychological diseases can decrease the intensity of the TGI. Because the TGI corresponds to chronic centralized pain, we believe that the findings of previous studies can be applied to future studies to identify chronic pain mechanisms and clinical practice for pain management.

Effectiveness Comparison of Using Macintosh Blade and Mccoy Blade For Endotracheal Intubation In Anesthesia Residents

Introduction: Laryngoscopy is one of the critical points in the intubation process and a mechanical trauma that provides noxious stimulation, affecting cardiovascular, respiratory, and intracranial changes. Practitioner competence is a significant factor that supports laryngoscope intubation procedures. That can influence the intubation duration and amount of mechanical trauma besides caused by laryngoscope type. Objective: To analyze the effectiveness of using Macintosh blade compared to McCoy blade in intubation laryngoscopy by Anesthesia Residents. Materials and Methods: This research is an experimental study in adult patients who underwent elective surgery at GBPT Dr. Soetomo Hospital. Intubation did by Anesthesia Residents at levels 5-9 using Macintosh or McCoy Laryngoscope and chosen randomly. The data of laryngeal visualization (Cormack Lehane), hemodynamics (blood pressure, pulse), pain scale (qNOX), intubation time length, and pain scale data (VAS) after extubation were taken during intubation laryngoscope. Result and Discussion: The study was conducted on 28 samples that met the criteria. Anesthesia Resident's competence levels based on the semester in both groups laryngoscopes were not different (p 0.868). Based on laryngeal visualization data laryngoscopy, the McCoy's blade had better visualization with CL 1 at 85.7% of the samples and p-value 0.020. This good visualization makes it possible to speed up the laryngoscope-intubation in the McCoy blade group with a significant difference of time compared to the Macintosh blade group. Hemodynamic parameters, there were significant differences for hemodynamics increase. In the Macintosh blade group, the blood pressure and pulse were significantly increased after laryngoscopy intubation. The pain scale during the intubation procedure, which was rated based on the qNOx score, showed a significant increase in the Macintosh blade group with a p-value of 0.003. The postoperative pain scale (VAS) was smaller in the McCoy blade group compared to the Macintosh group (p-value <0.001). Conclusion: The ability to use both laryngoscopes at some levels of Anesthesia residents was equally good, and the use of McCoy Blade is more effective than Macintosh Blade in the intubation laryngoscopy procedure.

The impact of premature extrauterine exposure on infants' stimulus-evoked brain activity across multiple sensory systems

Prematurity can result in widespread neurodevelopmental impairment, with the impact of premature extrauterine exposure on brain function detectable in infancy. A range of neurodynamic and haemodynamic functional brain measures have previously been employed to study the neurodevelopmental impact of prematurity, with methodological and analytical heterogeneity across studies obscuring how multiple sensory systems are affected. Here, we outline a standardised template analysis approach to measure the evoked response magnitudes for visual, tactile, and noxious stimulation within individual infants (n=15) using EEG. By studying a cohort of very preterm infants longitudinally (n=10), we observe that the evoked response template magnitudes are significantly associated with age-related maturation. In a subsequent cross-sectional study, we observe significant differences in visual and tactile response template magnitudes between infants born in the very preterm and late preterm periods (n=10 and 8), age-matched at study. These findings demonstrate the significant impact of premature extrauterine exposure on brain function and suggest that prematurity can accelerate maturation of the visual and tactile sensory system in infants born very prematurely. This study highlights the value of using a standardised multi-modal evoked-activity analysis approach to assess premature neurodevelopment, and will likely complement resting-state EEG and behavioural assessments in the study of the functional impact of developmental care interventions.

Copy neutral absence of heterozygosity on chromosome 15 distal long arm: A surrogate marker for Prader–Willi/Angelman syndromes?

Background Copy-neutral absence of heterozygosity (CN-AOH) observed on a single chromosome or part of a chromosome may be indicative of uniparental disomy (UPD) and may require additional testing when such chromosomes or chromosome regions are known to harbor imprinted genes. Case presentation Here we report 2 cases of neonates that presented to clinic with hypotonia, poor oral skills including inability to feed by mouth, weak cry, no response to noxious stimulation and vertical plantar creases (case 1) and hypotonia and respiratory distress (case 2). A preliminary chromosome analysis showed normal karyotypes in both cases while the high-resolution single nucleotide polymorphism (SNP) microarray showed copy neutral absence of heterozygosity involving chromosome 15 distal long arm. In case 1, the CN-AOH involved a 28.7 Mb block from genomic coordinates 73703619_102429049. In case 2, the CN-AOH involved a 15.3 Mb block from genomic coordinates 54729197_70057534. In both cases, methylation-specific PCR did not detect an unmethylated allele for the SNRPN gene suggesting either a deletion of paternal allele or maternal UPD for chromosome 15. Since microarray analysis did not show any copy number alterations on chromosome 15, a microdeletion was ruled out. Conclusions Based on our cases, we suggest that CN-AOH on chromosome 15, even if it does not involve the critical region of 15q12q13, should warrant additional studies for diagnosis of Prader–Willi/Angelman syndromes.

Role of SIRT1 in Neuropathic Pain from the Viewpoint of Neuroimmunity

: The current clinical first-line treatment of neuropathic pain still considers only the nervous system as the target, and its therapeutic effect is limited. An increasing number of studies support the opinion that neuropathic pain is a result of the combined action of the sensory nervous system and the related immune system. Under physiological conditions, both the nervous system and the immune system can maintain homeostasis by adjusting the mitochondrial function when sensing noxious stimulation. However, in the case of neuropathic pain, mitochondrial regulatory dysfunction occurs, which may result from the decreased expression of SIRT1. In this study, we review the role of SIRT1 in neuropathic pain from the viewpoint of neuroimmunity.

Functional and diffusion MRI reveal the neurophysiological basis of neonates’ noxious-stimulus evoked brain activity

Understanding the neurophysiology underlying neonatal responses to noxious stimulation is central to improving early life pain management. In this neonatal multimodal MRI study, we use resting-state and diffusion MRI to investigate inter-individual variability in noxious-stimulus evoked brain activity. We observe that cerebral haemodynamic responses to experimental noxious stimulation can be predicted from separately acquired resting-state brain activity (n=18). Applying this prediction model to independent Developing Human Connectome Project data (n=215), we identify negative associations between predicted noxious-stimulus evoked responses and white matter mean diffusivity. These associations are subsequently confirmed in the original noxious stimulation paradigm dataset, validating the prediction model. Here, we observe that noxious-stimulus evoked brain activity in healthy neonates is coupled to resting-state activity and white matter microstructure, that neural features can be used to predict responses to noxious stimulation, and that the dHCP dataset could be utilised for future exploratory research of early life pain system neurophysiology.

Gelsemium effect against nerve injury-induced mechanical allodynia and hyperalgesia

Background Gelsemium dilutions are prescribed for their anxiolytic and its analgesic effects. Investigations using alkaloids isolated from Gelsemium support the hypothesis of Gelsemium-induced analgesia. Aims We evaluated the antinociceptive effect of Gelsemium dilutions 3, 5 and 9C in neuropathic models. Methodology To investigate the potential effect of Gelsemium dilutions 3, 5 and 9C to prevent or to correct sciatic nerve chronic constriction (CCI) injury, we used the von-Frey hair behavioral test. CCI-induced neuropathic pain in rats represents characteristic painful behaviors like hyperalgesia and allodynia, thus validating its suitability for the evaluation of anti-neuropathic drugs. To test the corrective effect, Gelsemium 3, 5 or 9 C or placebo were administered from Day 14 after sciatic nerve ligation, i.e., when neuropathic symptoms were observed. In the preventive strategy, Gelsemium dilutions and placebo began immediately after the sciatic nerve ligation (D0). Results and discussion We observed that in placebo groups, the mechanical-sensitivity thresholds remained unchanged all treatment days whereas Gelsemium dilutions 3C and 5C exerted a strong or moderate antinociceptive effect, respectively. In CCI-rats, the contralateral paw of placebo-treated animals did not respond to 4g non-noxious stimulation but the ipsilateral responses increased progressively (0%-D0, 52%-D14, 72%-D21 and 88%-D28), confirming the occurrence of allodynia. Gelsemium dilution 3C corrective and preventive treatments efficiently reduced the allodynic responses (72-to-38%-D21 and 88-to-22%-D28). Gelsemium 5C also exhibited significant anti-allodynic action while Gelsemium 9C was ineffective. Similarly, one week treatment with Gelsemium 3 or 5C efficiently reduced 15g or 26g-evoked hyperalgesia and the beneficial action improved after 2 weeks. Chronic therapies with current analgesics induce several side-effects. Conclusion The present work, suggest that Gelsemium dilutions devoid of toxicity and used as anxiolytic in humans induced analgesia, opens interesting/alternative perspectives for long-term management of pain without undesirable effects.