The Dorsal Column Nuclei Scale Mechanical Sensitivity in Naive and Neuropathic Pain States.

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

Multimodal sensory control of motor performance by glycinergic interneurons of the mouse spinal cord deep dorsal horn.

Sensory feedback is integral for contextually appropriate motor output, yet the neural circuits responsible remain elusive. Here, we pinpoint the medial deep dorsal horn of the mouse spinal cord as a convergence point for proprioceptive and cutaneous input. Within this region, we identify a population of tonically active glycinergic inhibitory neurons expressing parvalbumin. Using anatomy and electrophysiology, we demonstrate that deep dorsal horn parvalbumin-expressing interneuron (dPV) activity is shaped by convergent proprioceptive, cutaneous, and descending input. Selectively targeting spinal dPVs, we reveal their widespread ipsilateral inhibition onto pre-motor and motor networks and demonstrate their role in gating sensory-evoked muscle activity using electromyography (EMG) recordings. dPV ablation altered limb kinematics and step-cycle timing during treadmill locomotion and reduced the transitions between sub-movements during spontaneous behavior. These findings reveal a circuit basis by which sensory convergence onto dorsal horn inhibitory neurons modulates motor output to facilitate smooth movement and context-appropriate transitions.

A new Hoxb8FlpO mouse line for intersectional approaches to dissect developmentally defined adult sensorimotor circuits.

Improvements in the speed and cost of expression profiling of neuronal tissues offer an unprecedented opportunity to define ever finer subgroups of neurons for functional studies. In the spinal cord, single cell RNA sequencing studies support decades of work on spinal cord lineage studies, offering a unique opportunity to probe adult function based on developmental lineage. While Cre/Flp recombinase intersectional strategies remain a powerful tool to manipulate spinal neurons, the field lacks genetic tools and strategies to restrict manipulations to the adult mouse spinal cord at the speed at which new tools develop. This study establishes a new workflow for intersectional mouse-viral strategies to dissect adult spinal function based on developmental lineages in a modular fashion. To restrict manipulations to the spinal cord, we generate a brain-sparing Hoxb8FlpO mouse line restricting Flp recombinase expression to caudal tissue. Recapitulating endogenous Hoxb8 gene expression, Flp-dependent reporter expression is present in the caudal embryo starting day 9.5. This expression restricts Flp activity in the adult to the caudal brainstem and below. Hoxb8FlpO heterozygous and homozygous mice do not develop any of the sensory or locomotor phenotypes evident in Hoxb8 heterozygous or mutant animals, suggesting normal developmental function of the Hoxb8 gene and protein in Hoxb8FlpO mice. Compared to the variability of brain recombination in available caudal Cre and Flp lines, Hoxb8FlpO activity is not present in the brain above the caudal brainstem, independent of mouse genetic background. Lastly, we combine the Hoxb8FlpO mouse line with dorsal horn developmental lineage Cre mouse lines to express GFP in developmentally determined dorsal horn populations. Using GFP-dependent Cre recombinase viruses and Cre recombinase-dependent inhibitory chemogenetics, we target developmentally defined lineages in the adult. We show how developmental knock-out versus transient adult silencing of the same ROR𝛃 lineage neurons affects adult sensorimotor behavior. In summary, this new mouse line and viral approach provides a blueprint to dissect adult somatosensory circuit function using Cre/Flp genetic tools to target spinal cord interneurons based on genetic lineage.

Deep Learning-Based Yoga Posture Recognition Using the Y_PN-MSSD Model for Yoga Practitioners.

In today's digital world, and in light of the growing pandemic, many yoga instructors opt to teach online. However, even after learning or being trained by the best sources available, such as videos, blogs, journals, or essays, there is no live tracking available to the user to see if he or she is holding poses appropriately, which can lead to body posture issues and health issues later in life. Existing technology can assist in this regard; however, beginner-level yoga practitioners have no means of knowing whether their position is good or poor without the instructor's help. As a result, the automatic assessment of yoga postures is proposed for yoga posture recognition, which can alert practitioners by using the Y_PN-MSSD model, in which Pose-Net and Mobile-Net SSD (together named as TFlite Movenet) play a major role. The Pose-Net layer takes care of the feature point detection, while the mobile-net SSD layer performs human detection in each frame. The model is categorized into three stages. Initially, there is the data collection/preparation stage, where the yoga postures are captured from four users as well as an open-source dataset with seven yoga poses. Then, by using these collected data, the model undergoes training where the feature extraction takes place by connecting key points of the human body. Finally, the yoga posture is recognized and the model assists the user through yoga poses by live-tracking them, as well as correcting them on the fly with 99.88% accuracy. Comparatively, this model outperforms the performance of the Pose-Net CNN model. As a result, the model can be used as a starting point for creating a system that will help humans practice yoga with the help of a clever, inexpensive, and impressive virtual yoga trainer.

Touch neurons underlying dopaminergic pleasurable touch and sexual receptivity.

Pleasurable touch is paramount during social behavior, including sexual encounters. However, the identity and precise role of sensory neurons that transduce sexual touch remain unknown. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice. Here, we study the social relevance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain. Even in social isolation, optogenetic stimulation of Mrgprb4-lineage neurons through the back skin is sufficient to induce a conditioned place preference and a striking dorsiflexion resembling the lordotic copulatory posture. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding: sexual receptivity is supplanted by aggression and a coincident decline in dopamine release in the nucleus accumbens. Together, these findings establish that Mrgprb4-lineage neurons initiate a skin-to-brain circuit encoding the rewarding quality of social touch.

Ultrasound-Guided Erector Spinae Block for Refractory Abdominal Pain Due to Acute on Chronic Pancreatitis.

Erector spinae blocks (ESBs) are a type of fascial pain block that has been safely used for various applications, including post-operative and post-trauma pain in several thoracic and abdominal surgeries. Pain related to an acute flare-up of chronic pancreatitis is usually challenging to control and impacts patient comfort and discharge planning. This case report describes an application of ESBs for the effective treatment of refractory abdominal pain associated with acute exacerbation of chronic pancreatitis. Application of ESB in the emergency room setting can potentially decrease hospital admission for this common condition and increase patient satisfaction.

A Microbiological Assay of Common Operating Room (OR) Tapes: Developing a Culture for Patient Safety.

BACKGROUND: There are no existing practices or methods to ensure cleanliness, sterility, or prevent cross-contamination when it comes to common operating room (OR) tape. The authors hypothesized that adhesive tapes used by anesthesia providers in ORs and off-site surgical areas might be colonized by microorganisms and that culturing these tape rolls would reveal significant monomicrobial and polymicrobial contamination.  Material and Methods: The primary objective of this observational cohort study was to report and compare contamination rate including polymicrobial contamination rate between tape specimens collected from storage site and specimen from the ORs, off-sites, and after use on a patient. The outcome measures were the culture reports of the adhesive tapes. The authors then designed an intervention that integrated anesthesia providers' hand hygiene and maintenance of a barrier between the OR tapes and OR surfaces. RESULTS: The authors reported gross contamination and cross-contamination among the OR off-site tapes. The contamination rates reported for tapes from OR, off-site specimens, and patient specimens were 68.2%,63.2%, and 100%, respectively. The authors again cultured adhesive tapes after the intervention and reported improved outcomes. CONCLUSIONS: The current quality improvement (QI) project identified the potential for OR tapes to serve as microbial vectors. The authors advocate environmental decontamination and anesthesia providers' hand hygiene in parallel as a part of routine anesthesia care in their practice and agree that the endotracheal tubes (ETTs) and orogastric or nasogastric tubes should be pre-packaged with single-use tape, which can be used for securing devices.

Stellate Ganglion Block for Anosmia and Dysgeusia Due to Long COVID.

Anosmia and parosmia refer to the loss or dysfunction of smell, respectively. Dysgeusia refers to taste disturbance. The coronavirus disease 2019 (COVID-19) pandemic and the subsequent phenomenon of Long COVID syndrome have been associated with an increased incidence of anosmia and dysgeusia. Smell and taste disturbances associated with COVID-19 are usually self-limiting but can persist for longer periods in some cases. Imbalances of the autonomic nervous system, especially dysregulation of the sympathetic system, are implicated in the persistence of anosmia and dysgeusia post-COVID-19 infection. Stellate ganglion block (SGB) can diminish the increased sympathetic activity and potentially resolve anosmia and dysgeusia occurring due to Long COVID. The authors report the successful resolution of persistent anosmia and dysgeusia due to Long COVID in a female patient after she underwent SGB.

The Effects of Streptozotocin-Induced Diabetes and Insulin Treatment on Carnitine Biosynthesis and Renal Excretion.

Carnitine insufficiency is reported in type 1 diabetes mellitus. To determine whether this is accompanied by defects in biosynthesis and/or renal uptake, liver and kidney were obtained from male Sprague-Dawley rats with streptozotocin-induced diabetes. Diabetic rats exhibited the metabolic consequences of type 1 diabetes, including hypoinsulinemia, hyperglycemia, and increased urine output. Systemic hypocarnitinemia, expressed as free carnitine levels, was evident in the plasma, liver, and kidney of diabetic rats. Compared to control rats, the low free carnitine in the plasma of diabetic rats was accompanied by decreased expression of γ-butyrobetaine hydroxylase in liver and kidney, suggesting impaired carnitine biosynthesis. Expression of organic cation transporter-2 in kidney was also reduced, indicating impaired renal reabsorption, and confirmed by the presence of elevated levels of free carnitine in the urine of diabetic rats. Insulin treatment of diabetic rats reversed the plasma hypocarnitinemia, increased the free carnitine content in both kidney and liver, and prevented urinary losses of free carnitine. This was associated with increased expression of γ-butyrobetaine hydroxylase and organic cation transporter-2. The results of our study indicate that type 1 diabetes induced with streptozotocin disrupts carnitine biosynthesis and renal uptake mechanisms, leading to carnitine insufficiency. These aberrations in carnitine homeostasis are prevented with daily insulin treatment.

Development and Investigation of an Inexpensive Low Frequency Vibration Platform for Enhancing the Performance of Electrical Discharge Machining Process.

Difficulty in debris removal and the transport of fresh dielectric into discharge gap hinders the process performance of electrical discharge machining (EDM) process. Therefore, in this work, an economical low frequency vibration platform was developed to improve the performance of EDM through vibration assistance. The developed vibratory platform functions on an eccentric weight principle and generates a low frequency vibration in the range of 0-100 Hz. The performance of EDM was evaluated in terms of the average surface roughness (Ra), material removal rate (MRR), and tool wear rate (TWR) whilst varying the input machining parameters viz. the pulse-on-time (Ton), peak current (Ip), vibration frequency (VF), and tool rotational speed (TRS). The peak current was found to be the most significant parameter and contributed by 78.16%, 65.86%, and 59.52% to the Ra, MRR, and TWR, respectively. The low frequency work piece vibration contributed to an enhanced surface finish owing to an improved flushing at the discharge gap and debris removal. However, VF range below 100 Hz was not found to be suitable for the satisfactory improvement of the MRR and reduction of the TWR in an electrical discharge drilling operation at selected machining conditions.

Effects of Exercise Training on Renal Carnitine Biosynthesis and Uptake in the High-Fat and High-Sugar-Fed Mouse.

(1) Background: Diet-induced obesity inhibits hepatic carnitine biosynthesis. Herein, the effects of high-fat (HF) and high-sugar (HFHS) feeding and exercise training (ET) on renal carnitine biosynthesis and uptake were determined. (2) Methods: Male C57BL/6J mice were assigned to the following groups: lean control (standard chow), HFHS diet, and HFHS diet with ET. ET consisted of 150 min of treadmill running per week for 12 weeks. Protein levels of γ-butyrobetaine hydroxylase (γ-BBH) and organic cation transporter-2 (OCTN2) were measured as markers of biosynthesis and uptake, respectively. (3) Results: HFHS feeding induced an obese diabetic state with accompanying hypocarnitinemia, reflected by decreased free carnitine levels in plasma and kidney. This hypocarnitinemia was associated with decreased γ-BBH (~30%) and increased OCTN2 levels (~50%). ET failed to improve the obesity and hyperglycemia, but improved insulin levels and prevented the hypocarnitinemia. ET increased protein levels of γ-BBH, whereas levels of OCTN2 were decreased. Peroxisome proliferator-activated receptor-alpha content was not changed by the HFHS diet or ET. (4) Conclusions: Our results indicate that ET prevents the hypocarnitinemia induced by HFHS feeding by increasing carnitine biosynthesis in kidney. Increased expression of OCTN2 with HFHS feeding suggests that renal uptake was stimulated to prevent carnitine loss.

Optogenetic and transcriptomic interrogation of enhanced muscle function in the paralyzed mouse whisker pad.

The functional state of denervated muscle is a critical factor in the ability to restore movement after injury- or disease-related paralysis. Here we used peripheral optogenetic stimulation and transcriptome profiling in the mouse whisker system to investigate the time course of changes in neuromuscular function following complete unilateral facial nerve transection. While most skeletal muscles rapidly lose functionality after lower motor neuron denervation, optogenetic muscle stimulation of the paralyzed whisker pad revealed sustained increases in the sensitivity, velocity, and amplitude of whisker movements, and reduced fatigability, starting 48 h after denervation. RNA-seq analysis showed distinct regulation of multiple gene families in denervated whisker pad muscles compared with the atrophy-prone soleus, including prominent changes in ion channels and contractile fibers. Together, our results define the unique functional and transcriptomic landscape of denervated facial muscles and have general implications for restoring movement after neuromuscular injury or disease. NEW & NOTEWORTHY Optogenetic activation of muscle can be used to noninvasively induce movements and probe muscle function. We used this technique in mice to investigate changes in whisker movements following facial nerve transection. We found unexpectedly enhanced functional properties of whisker pad muscle following denervation, accompanied by unique transcriptomic changes. Our findings highlight the utility of the mouse whisker pad for investigating the restoration of movement after paralysis.

A Randomized Controlled Trial of Fluoroscopically-Guided Sacroiliac Joint Injections: A Comparison of the Posteroanterior and Classical Oblique Techniques.

OBJECTIVE: The sacroiliac joint can be a primary source of pain or part of multifactorial syndromes. As there is no single historical, physical examination-based, or radiological feature that definitively establishes a diagnosis of sacroiliac joint pain, diagnostic blocks are regarded as the gold standard. The primary aim of this randomized trial was to compare the posteroanterior approach with the classic oblique approach for sacroiliac joint injection based on an assessment of procedure times and patient-reported pain outcomes in subjects scheduled for fluoroscopically-guided sacroiliac joint injections. METHODS: Thirty patients were randomized into 2 groups of 15 patients each. The endpoints measured included the total length of procedure time, fluoroscopic time, needling time (length of time the needle was maneuvered), and pre- and postprocedure visual analogue scale pain scores. RESULTS: The posteroanterior approach was significantly shorter in terms of procedure time (p=0.03) and needling time (p=0.01) than the oblique approach. Adjusting for body mass index, the mean procedure and needling times were significantly shorter in the posteroanterior group than in the oblique group. CONCLUSION: This study of the posteroanterior approach for fluoroscopic-guided sacroiliac joint injection observed shorter times for fluoroscopy, needling, and the overall procedure than were recorded for the widely prevalent oblique approach. This may translate to lower radiation exposure, lower procedural costs, and enhanced ergonomics of fluoroscopicallyguided sacroiliac joint injections.

Retrospective Review of Magnetic Resonance Imaging of the Lumbosacral Spine: Are We Overinvestigating?

OBJECTIVE: Lower back pain (LBP) is a worldwide health problem, and magnetic resonance imaging (MRI) is a common modality used to aid in its diagnosis. Although specific guidelines for assessing the necessity of MRI usage exist, the use of MRI as the initial imaging method for LBP seems to be more common than necessary in general practice. METHODS: We conducted a retrospective chart review of 313 patients who had undergone MRI of the lumbosacral spine during 2014-2015. We recorded and compared various factors, including age, sex, body mass index, current smoking status, race, symptoms, MRI findings, and progression to surgery within the next year. All rates were compared according to whether the MRI results showed radiographically significant findings (MRI-positive) or not (MRI-negative) using the chi-square or Fisher exact tests (if the expected cell count was <5). All analyses were performed using SAS version 9.4. RESULTS: There were no statistically significant differences in the rates of each symptom between the MRI-positive and MRI-negative groups, which accounted for 58.5% (183 of 313) and 41.5% (130 of 313) of the MRIs, respectively. The difference in the rate of surgery in the next year (18% among MRI-positive patients and 8.5% among MRI-negative patients) was found to be statistically significant (p<0.05). CONCLUSION: Based on our findings, 41.5% of patients underwent lumbar MRI unnecessarily and 81% of patients with positive MRIs did not have surgery within the next year. Further physician training is needed to avoid unnecessary investigations and expenditures.

Radiofrequency Ablation of the Sphenopalatine Ganglion Using Cone Beam Computed Tomography for Intractable Cluster Headache.

UNLABELLED: Percutaneous radiofrequency ablation (RFA) of the sphenopalatine ganglion (SPG) has been shown to be an effective modality of treatment for patients with intractable chronic cluster headaches (CHs). While the use of fluoroscopy for RFA of the SPG is common, to our knowledge there are no documented cases of procedures using cone beam computed tomography (CBCT) for image guidance. We present a case report of a patient suffering from chronic intractable CH with complete long-lasting relief after RFA of the SPG using CBCT. The case reaffirms the potential efficacy of RFA of the SPG in a case of chronic cluster headache as well as the use of CBCT as a superior alternative to bi-plane fluoroscopy for image guidance in the management of chronic CH. KEY WORDS: Cone beam computed tomography, sphenopalatine ganglion block, cluster headache, interventional pain, autonomic cephalalgia, radiofrequency ablation.

Clostridium Sacroiliitis (Gas Gangrene) Following Sacroiliac Joint Injection--Case Report and Review of the Literature.

An 80-year-old woman presented with chronic lumbosacral pain since her laminectomy and instrumentation 10 years ago. Examination was consistent with left sacroiliitis, and the patient underwent an elective left sacroiliac joint injection. Two days following her procedure she fell and landed on her left hip and on the next day, she presented to the emergency room with acutely worsening left gluteal pain. On evaluation in the emergency department, she was found to be suffering from a fever, headache, nausea, vomiting, and dysuria. A computed tomography (CT) scan was performed and this showed extensive foci of gas throughout the posterior aspect of the left iliopsoas muscle, sacrum, and ileum surrounding the left sacroiliac joint. The patient underwent emergent surgical debridement. The microbiology report of blood culture revealed clostridium perfringens, while her pathology showed necrosis and acute inflammation of fibroadipose tissue, skeletal muscle, and fat. The patient's hospital course resulted in multi-organ failure and the family elected for comfort care measures only. Unfortunately, she passed away 36 hours later. Septic arthritis is a potential catastrophic complication following intra-articular steroid therapy. The cause of the septic joint can be multifactorial but is likely caused by one of the following processes: direct inoculation of bacteria by the injection, hematogenous seeding of the percutaneous injection tract, or due to activation of a quiescent infection by the injected steroid. Clostridial spores are very resistant to standard aseptic skin preparations, including chlorhexidine and betadine solutions. The only effective methods to eliminate the spores is to heat them at a temperature greater than 100 degrees Celsius for 10 minutes or with use of a 10% potassium hydroxide (KOH) solution. We hypothesize that clostridium spores were present on the patient's skin from previous stool soiling, and that these were introduced directly into the soft tissue by needle trauma. Rare complications such as this one are scarcely reported in the literature and thus it becomes difficult to adequately identify risk factors or to formulate strategies to improve practice management.