Recent ucsdsom_an_oapdeposits items

Effects of Noninvasive Cervical Vagal Nerve Stimulation on Cognitive Performance But Not Brain Activation in Healthy Adults

Wed, 29 Apr 2026 00:00:00 +0000

OBJECTIVES: While preliminary evidence suggests that noninvasive vagal nerve stimulation (nVNS) may enhance cognition, to our knowledge, no study has directly assessed the effects of nVNS on brain function and cognitive performance in healthy individuals. The aim of this study was therefore to assess whether nVNS enhances complex visuospatial problem solving in a normative sample. Functional magnetic resonance imaging (fMRI) was used to examine underlying neural substrates. MATERIAL AND METHODS: Participants received transcutaneous cervical nVNS (N = 15) or sham (N = 15) stimulation during a 3 T fMRI scan. Stimulation lasted for 2 min at 24 V for nVNS and at 4.5 V for sham. Subjects completed a matrix reasoning (MR) task in the scanner and a forced-choice recognition task outside the scanner. An analysis of variance (ANOVA) was used to assess group differences in cognitive performance. And linear mixed effects (LMEs) regression analysis was used to assess main and interaction...

Distinct effects of fibromyalgia pain, depression and anxiety on perception of affective touch and pain

Thu, 9 Apr 2026 00:00:00 +0000

Gentle stroking that activates C-tactile afferents is typically pleasant, calming and pain relieving. Deep pressure touch frequently elicits similar affective responses. However touch is often less pleasant for individuals with chronic pain. It is important to understand the reasons for this clinical difference because of the close relationship of pain with reduced social connection, and the widespread use of touch-based therapies for pain relief. It is not known whether differences in touch perception in chronic pain relate to pain-specific processes or to comorbid affective symptoms. The current study compared affective touch perception in adults with the chronic pain condition fibromyalgia (FM) and no-pain (NP) controls, and the contributions of pain, depression, anxiety and trauma history to differences in touch perception. We hypothesized that deep pressure - like gentle stroking - would be less pleasant in FM and that these differences would be associated with depression...

Accuracy and precision of minimally-invasive cardiac output monitoring in children: a systematic review and meta-analysis

Thu, 26 Feb 2026 00:00:00 +0000

Abstract Several minimally-invasive technologies are available for cardiac output (CO) measurement in children, but the accuracy and precision of these devices have not yet been evaluated in a systematic review and meta-analysis. We conducted a comprehensive search of the medical literature in PubMed, Cochrane Library of Clinical Trials, Scopus, and Web of Science from its inception to June 2014 assessing the accuracy and precision of all minimally-invasive CO monitoring systems used in children when compared with CO monitoring reference methods. Pooled mean bias, standard deviation, and mean percentage error of included studies were calculated using a random-effects model. The inter-study heterogeneity was also assessed using an I2 statistic. A total of 20 studies (624 patients) were included. The overall random-effects pooled bias, and mean percentage error were 0.13 ± 0.44 l min−1 and 29.1 %, respectively. Significant inter-study heterogeneity was detected...

Expanding Access to Vascular Imaging: Preliminary Results from the Development of a Remote Surveillance Device

Wed, 25 Feb 2026 00:00:00 +0000

Introduction/Objectives Patients undergoing surgical procedures for peripheral artery disease and carotid artery stenosis are recommended to undergo surveillance imaging at regular intervals. With > 250,000 patients undergoing interventions for both annually, the number of patients requiring interval surveillance increases in parallel, placing strain on an already overburdened health system. In this study we evaluated the performance of a novel ultrasound platform prototype built for remote ultrasound surveillance. Methods The prototype duplex ultrasound device was developed by a team of engineers and utilizes color flow images to detect the vessel for flow velocity measurements. The device was tested on 28 healthy volunteers. The results of spectral flow from the device were compared to standard of care ultrasound measurements of the CFA, SFA, ICA and CCA. Results The mean absolute difference between the prototype ultrasound and standard of care device for peak systolic velocity...

Medical cannabis authorization and opioid milligram equivalents over time in patients with chronic pain: a retrospective analysis

Thu, 29 Jan 2026 00:00:00 +0000

OBJECTIVE: Strategies are needed for patients with chronic pain who are using opioids to safely and effectively wean opioids without worsening of pain. The objective was to measure associations between medical cannabis authorization (MCA) and opioid milligram equivalents (OME) in patients with chronic non-cancer pain. DESIGN: A longitudinal, retrospective cohort analysis from July 2016 to August 2019. SETTING: Electronic health record data were analyzed. SUBJECTS: Adult patients (≥18 years) seen in a university-based pain clinic. METHODS: Longitudinal multilevel modeling with maximum likelihood estimation. RESULTS: Average overall OME at the final time point was 33.4 mg/day (SE = 1.18) with increase over time of 0.45 mg/day per quarter (not statistically significant). Average OME in those without MCA was 32.60 mg/day (SE = 1.11) versus 38.51 mg/day (SE = 4.81) in those with MCA, not significantly different. Medical cannabis consultation predicted a nonsignificant decrease of 14.25 mg/day...

Cannabis use disorder and mortality among patients with colon cancer

Thu, 4 Dec 2025 00:00:00 +0000

Cannabis use disorder and mortality among patients with colon cancer

Diabetes medications and dementia risk: Comparisons of SGLT2 inhibitors, GLP-1 RAs, metformin, and their combinations

Thu, 4 Dec 2025 00:00:00 +0000

Background Type 2 diabetes (T2D) elevates dementia risk through vascular injury, neuroinflammation, and perturbed insulin signaling. Antidiabetic classes differ in extra-glycemic actions that could modify neurodegeneration, yet head-to-head comparative data remain limited. Objective To compare time to incident dementia among older adults with T2D exposed to SGLT2 inhibitors, GLP-1 receptor agonists (GLP-1 RAs), metformin, or two-way combinations, and to quantify the contribution of comorbidities and neuroactive co-medications. Methods We performed a retrospective cohort study in the UCHDW (2012–2024). Adults aged 55–80 were assigned to the earliest qualifying exposure group and followed from index to first coded Alzheimer’s disease or unspecified dementia; vascular/multi-infarct dementias were excluded by design to reduce etiologic heterogeneity. Events recorded within 84 days of index were not considered incident outcomes (individuals were retained and censored at 84 days). Covariates...

Influence of Substance Use Disorders on Mortality in a Systemwide Cohort of Cancer Patients

Thu, 4 Dec 2025 00:00:00 +0000

BACKGROUND: Cancer treatment is often complicated by co-occurring substance dependence such as alcohol, cannabis, opioids, amphetamines, and tobacco. The objective of this study was to analyze the association between substance use (alcohol, cannabis, opioids, amphetamines, and tobacco) and mortality among cancer patients. METHODS: This retrospective study used de-identified data from the University of California, San Diego Health on 22,763 cancer patients aged ≥ 18 years. Substance dependance post-diagnosis was identified based on clinical observations from electronic health records. Tumor staging was determined using the TNM system, with missing data imputed via biomarker-based regression. Cox proportional hazards models were computed to assess severity-adjusted associations between substance dependance, by type, and mortality. RESULTS: Cannabis dependence was not significantly associated with mortality. Alcohol, tobacco, opioid, and amphetamine dependence were linked...

The Influence of GLP-1 Receptor Agonists on Five-Year Mortality in Colon Cancer Patients

Thu, 4 Dec 2025 00:00:00 +0000

Colorectal cancer is a leading cause of morbidity and mortality worldwide. This study investigates the association between GLP-1 receptor agonists (GLP-1 RAs) and five-year mortality in patients with primary colon cancer, considering BMI. Using data from the University of California Health Data Warehouse, 6,871 patients were analyzed. Five-year mortality was 15.5% for GLP-1 RA users compared to 37.1% for non-users. Analyses showed significantly lower odds of five-year mortality with GLP-1 RA use (OR = 0.38, 95% CI: 0.21-0.64). This benefit persisted after adjusting for confounders, including disease severity, but was found to only extend to high obese patients (BMI > 35) in stratified modeling.

Cannabis use disorder and five-year risk of oral cancer in a multicenter clinical cohort

Thu, 4 Dec 2025 00:00:00 +0000

Objective: Cannabis use disorder (CUD) is increasingly prevalent in the United States, yet long-term health consequences remain poorly defined. Oral cancer is plausible given shared carcinogens between cannabis and tobacco. This study assessed associations between CUD and five-year oral cancer risk in a large clinical cohort. Methods: This retrospective cohort study analyzed clinical records from the University of California Health Data Warehouse, covering six academic medical centers. Adults screened for drug use disorders between January 2012 and December 2019 were included if they had no prior oral cancer diagnosis. The index date was the date of first screening. Patients were followed for five years for oral cancer diagnoses (lip or tongue), thereby extending data collection to December 2024. CUD was defined by a new ICD-coded diagnosis during follow-up. Logistic regression and Cox proportional hazards models estimated odds ratios (ORs), hazard ratios (HRs), and 95 %...

Mindfulness meditation reduces pain more effectively than slow-breathing meditation: the mediating role of respiration.

Mon, 10 Nov 2025 00:00:00 +0000

ABSTRACT: Mindfulness meditation, a slow breathing practice that is predicated on cultivating nonreactive awareness, also reduces pain. The existing literature has been mixed in demonstrating whether mindfulness meditation is more effective than slow breathing alone (ie, sham-mindfulness meditation) at reducing pain. Furthermore, smaller sample sizes in prior work have hindered a clear understanding of how respiration rate and state anxiety contribute to analgesia during meditation. This study pooled data from 5 randomized controlled trials using paralleling interventions and methodologies in 245 healthy, pain-free, meditation-naïve individuals. Noxious heat (49°C; right calf) was used to test whether changes in respiration and state anxiety mediate the effects of (1) mindfulness meditation (n = 113), (2) a slow-breathing sham-mindfulness meditation technique (n = 73), and (3) a book-listening control (n = 60) on pain intensity ratings ("0" no pain; "10" worst pain imaginable)....

Percutaneous analgesic device enabling both local anesthetic delivery and electrical stimulation (neuromodulation) of peripheral nerves: a pilot feasibility study (case series)

Thu, 6 Nov 2025 00:00:00 +0000

BACKGROUND: A novel device integrating both local anesthetic delivery and peripheral nerve stimulation (PNS) to treat postoperative pain is under development. The device uses a catheter-over-needle design that permits ultrasound-guided percutaneous insertion. An integrated electrode and pulse generator enable PNS for up to 28 days. Such an approach may represent a paradigm shift in postoperative pain management by enabling the delivery of (1) a single-injection peripheral nerve block, (2) a continuous peripheral nerve block, and (3) neuromodulation-all through a single system that can be placed in a timeframe comparable with that of a traditional single-injection nerve block. The current prospective pilot study was executed under a US Food and Drug Investigational Device Exemption to develop insertion and management protocols, as well as assess the feasibility and safety of using the device to treat postoperative pain. METHODS: Preoperatively, adults (n=20) undergoing moderate-to-severely...

Cryoanalgesia to treat phantom limb pain following a trans-femoral (above-knee) amputation: a randomized, sham-controlled pilot study

Thu, 23 Oct 2025 00:00:00 +0000

BACKGROUND: A previous clinical trial applied percutaneous cryoneurolysis to lower limb amputees with phantom pain. The primary outcome measure was negative, but a secondary analysis suggested that patients with a below-knee amputation (BKA) improved, while the opposite was true for above-knee amputations (AKA). We theorized two potential reasons for this difference: cryoneurolysis was inadequate for the larger sciatic nerve in the upper thigh for AKA versus the lower thigh for BKA; and BKA is innervated by only two nerves, both of which were treated while AKA involved two additional nerves left untreated. METHODS: Participants with an existing AKA and intractable phantom pain had four nerves treated with ultrasound-guided percutaneous cryoneurolysis in the upper thigh: sciatic, femoral, obturator, lateral femoral cutaneous. For the larger nerves, we used an argon-based machine capable of inducing temperatures as low as -100°C and producing a relatively large ice ball. The sciatic...

A GI‐Interoceptive Threat Theory of Restrictive Eating: Insights From Active Inference and Chronic Pain

Mon, 13 Oct 2025 00:00:00 +0000

INTRODUCTION: Restrictive eating is a common eating disorder (ED) behavior and risk factor. Disturbed body image is also highly associated with the development and maintenance of eating disorders. Yet body image often remains distorted after treatment, and there is little scientific understanding of the mechanisms by which restrictive eating and distorted body image are linked. In parallel, current models of chronic pain describe how fear and negative beliefs about pain lead to avoidance of painful sensations and a threatened response to their occurrence, entrenching a cycle of amplified pain that risks becoming chronic. These models are informed by theories of active inference, which describe how the brain actively shapes sensory experience to reduce prediction errors (discrepancy between predictions and sensory data). This understanding has led to significant advances in the treatment of chronic pain. METHODS: Theories of active inference and central sensitization in chronic...

Distinct somatic mutation profiles in colon cancer by behavioral comorbidity

Thu, 25 Sep 2025 00:00:00 +0000

BACKGROUND: Tobacco use, obesity, and type 2 diabetes are risk factors for colorectal cancer, but whether they generate distinct tumor mutation patterns is unclear. Tobacco is a known mutagen, while obesity and diabetes may act through metabolic and inflammatory pathways. METHODS: We analyzed colon cancer patients from the University of California Health Data Warehouse, linking clinical sequencing data to diagnosis-based indicators of tobacco dependence, obesity, and type 2 diabetes. For each gene-behavior pair, we conducted reverse logistic regressions and calculated a combined score reflecting the strength and specificity of association adjusting for demographic covariates and cancer stage. Multidimensional scaling and clustering assessed behavioral differentiation. RESULTS: Of 981 gene-behavior tests, 87 pairs exhibited a behavioral association at p < 0.001 in adjusted models. Of these, 60 tobacco, 12 obesity, and 9 diabetes pairs had affinity ≥0.5; 48 tobacco pairs...

Assessing the impact of environmental tobacco smoke on five-year cancer mortality

Thu, 25 Sep 2025 00:00:00 +0000

Background

Environmental tobacco smoke (ETS), also known as passive smoke, is a major public health concern due to its adverse health effects, which are comparable to those of active smoking. Although the risks of ETS for cardiovascular and respiratory outcomes are well documented, less is known about its impact on cancer prognosis. This study evaluated the association between ETS exposure and five-year all-cause mortality among patients diagnosed with breast, colorectal, lung, melanoma, or stomach cancer.

Methods

Clinical data were obtained from the UC San Diego Health system and the UC Health Data Warehouse. The study cohort included 17,729 adult patients with a confirmed cancer diagnosis and no recorded history of active smoking. ETS exposure and five-year mortality were identified using structured electronic health record data. Multivariable exact logistic regression and Cox proportional hazards models were used to estimate the association between ETS exposure...

Effect of warm pressure on feelings of social connection with close others

Tue, 16 Sep 2025 00:00:00 +0000

Social touch, such as hugging and hand-holding, may aid in the maintenance of feelings of social connection. Research on gentle stroking has demonstrated its social-affective effects. However, other elements of touch that might contribute to feelings of social connection are poorly understood. The current research seeks to determine the effect of warmth and pressure, given their involvement in social touch, on feelings of social connection with close others. In a 2 × 2 within-subjects experiment, 75 participants (M age = 19.89, 77.30 % women), were exposed to repeated trials of warm or neutral temperature packs, combined with deep or light pressure from weighted blankets, while they viewed images of close others. Feelings of social connection towards the pictured individuals were collected after each trial. After adjusting for age, there was an interaction such that warm deep pressure increased feelings of social connection compared to warm light pressure and neutral deep pressure....

Accuracy and precision of non-invasive cardiac output monitoring devices in perioperative medicine: a systematic review and meta-analysis † † This Article is accompanied by Editorial Aew442.

Tue, 2 Sep 2025 00:00:00 +0000

Cardiac output (CO) measurement is crucial for the guidance of therapeutic decisions in critically ill and high-risk surgical patients. Newly developed completely non-invasive CO technologies are commercially available; however, their accuracy and precision have not recently been evaluated in a meta-analysis. We conducted a systematic search using PubMed, Cochrane Library of Clinical Trials, Scopus, and Web of Science to review published data comparing CO measured by bolus thermodilution with commercially available non-invasive technologies including pulse wave transit time, non-invasive pulse contour analysis, thoracic electrical bioimpedance/bioreactance, and CO2 rebreathing. The non-invasive CO technology was considered acceptable if the pooled estimate of percentage error was <30%, as previously recommended. Using a random-effects model, sd, pooled mean bias, and mean percentage error were calculated. An I2 statistic was also used to evaluate the inter-study heterogeneity....

The Nutritional Epidemiology Risk–Survival Paradox

Thu, 28 Aug 2025 00:00:00 +0000

A foundational principle of nutritional epidemiology is that certain exposures, such as obesity, alcohol intake, and cholesterol, confer increased risk of chronic diseases. Yet growing evidence indicates that once diseases like cancer or cardiovascular disease are diagnosed, the same exposures may be associated with improved survival outcomes. This phenomenon, which may be considered a risk-survival paradox in nutritional epidemiology, challenges conventional dietary frameworks that assume continuity between disease prevention and disease prognosis. In this perspective article, I examine this paradox through a detailed analysis of 4 key exposures: obesity, alcohol, cholesterol, and antioxidant supplementation, restricted to cancer and cardiovascular disease. These 2 disease areas have the most extensive and methodologically diverse literature documenting risk-survival reversals and are responsible for the highest proportion of global mortality. Key limitations including reverse...

Ultrasound-Guided Percutaneous Cryoneurolysis for Perioperative Analgesia Following Major Lower Extremity Amputation: A Randomized, Participant- and Observer-Masked, Sham-Controlled Pilot Study

Thu, 14 Aug 2025 00:00:00 +0000

BACKGROUND: Extremity amputations are associated with pain in both the residual limb and the phantom limb. This pain, which is often debilitating, may be prevented by excellent perioperative pain control. Ultrasound-guided percutaneous cryoneurolysis is an analgesic modality offering pain control for weeks or months following surgery. This treatment has not been compared to the sham procedure for large nerves (e.g., femoral and sciatic) to provide preoperative analgesia. We therefore conducted a randomized, controlled pilot study to evaluate the use of this modality for the treatment of pain following amputation to (1) determine the feasibility of and optimize the study protocol for a subsequent definitive clinical trial; and (2) estimate analgesia and opioid reduction within the first postoperative weeks. METHODS: A convenience sample of seven patients undergoing lower extremity amputation were randomized to receive either active cryoneurolysis or a sham procedure targeting the...

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial

Thu, 14 Aug 2025 00:00:00 +0000

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants,...

Pulsed Shortwave (Radiofrequency) Therapy With a Noninvasive, Wearable, Disposable Device: A Randomized, Participant- and Assessor-Masked, Sham-Controlled Pilot Study

Thu, 14 Aug 2025 00:00:00 +0000

OBJECTIVES: Pulsed shortwave therapy (PSWT) is a nonpharmacologic/noninvasive modality that may offer analgesic benefits without notable side effects or complications. This pilot study aimed to assess the feasibility of a PSWT protocol and provide an estimate of its treatment effects. MATERIALS AND METHODS: The study included adults who underwent cholecystectomy or unilateral total hip or knee arthroplasty. Participants were randomized to eight days of either PSWT with a single functioning device (SofPulse, Endonovo Therapeutics, Woodland Hills, CA) or a sham device placed over the surgical bandages in a participant- and assessor-masked fashion. The primary end point was the sum of the average and worst (maximum) daily pain intensity as measured with the numeric rating scale collected over the first seven postoperative days. RESULTS: No systemic side effects or significant complications occurred. During the first seven postoperative days, the sum of the daily pain intensity scores...

Postoperative and postdischarge nausea and vomiting following ambulatory eye, head, and neck surgeries: a retrospective cohort study comparing incidence and associated factors

Thu, 14 Aug 2025 00:00:00 +0000

BackgroundAmbulatory surgery is often followed by the development of nausea and/or vomiting (N/V). Although risk factors for postoperative nausea and vomiting (PONV) are frequently discussed, the distinction between PONV and postdischarge nausea and vomiting (PDNV) is unclear. This is especially troublesome given the potential consequences of postdischarge nausea and vomiting (PDNV), which include major discomfort and hospital readmission.MethodsIn this retrospective cohort study, data from 10,231 adult patients undergoing ambulatory ophthalmology or otolaryngology procedures with general anesthesia were collected and analyzed. Binary and multinomial logistic regression was used to assess the association between patient and anesthetic characteristics (including age, body mass index (BMI), American Society of Anesthesiologists Physical Status (ASA P/S) classification, current smoker status, and intra- and postoperative opioid usage) and the odds ratios of experiencing only PDNV,...

Treating intractable postamputation pain with wearable, non-invasive, non-thermal, pulsed shortwave (radiofrequency) therapy: a randomized, double-masked, sham-controlled, crossover pilot study

Thu, 14 Aug 2025 00:00:00 +0000

Treating intractable postamputation pain with wearable, non-invasive, non-thermal, pulsed shortwave (radiofrequency) therapy: a randomized, double-masked, sham-controlled, crossover pilot study

Paravertebral versus Pectoralis-II (Interpectoral and Pectoserratus) Nerve Blocks for Postoperative Analgesia after Nonmastectomy Breast Surgery: A Randomized, Controlled, Observer-masked Noninferiority Trial

Thu, 14 Aug 2025 00:00:00 +0000

BACKGROUND: Pectoralis-II and paravertebral nerve blocks are both used to treat pain after breast surgery. Most previous studies involving mastectomy identified little difference of significance between the two approaches. Whether this is also accurate for nonmastectomy procedures remains unknown. METHODS: Participants undergoing uni- or bilateral nonmastectomy breast surgery anticipated to have at least moderate postoperative pain were randomized to a pectoralis-II or paravertebral block (90 mg ropivacaine per side for both). Surgeons and recovery room staff were masked to treatment group assignment, and participants were not informed of their treatment group. Injectate for pectoralis-II blocks was ropivacaine 0.3% (30 ml) per side. Injectate for paravertebral blocks was ropivacaine 0.5% (9 ml in each of two levels) per side. This study hypothesized that pectoralis-II blocks would have noninferior analgesia (numeric rating scale) and noninferior cumulative opioid consumption...

Percutaneous auricular neuromodulation to treat pain after ambulatory breast surgery: A randomized, double-masked, sham-controlled pilot study

Thu, 14 Aug 2025 00:00:00 +0000

Introduction: Percutaneous auricular neuromodulation involves implanting electrodes around the ear and administering an electric current. A device is currently available that is cleared to treat symptoms from opioid withdrawal, and multiple reports suggest a possible postoperative analgesic effect. This randomized, controlled pilot study aimed to (1) assess the feasibility of a postoperative auricular neuromodulation protocol and (2) provide an estimate of its treatment effects on postoperative pain and opioid consumption. Methods: Adults undergoing unilateral or bilateral ambulatory breast surgery with anticipated moderate-severe pain and a single-injection paravertebral nerve block(s) received an auricular neuromodulation device (NSS-2 Bridge, Masimo) following surgery. Participants were randomized to 5 days of electrical stimulation or sham in a double-masked fashion. Results: In the first 5 days, the median pain for those receiving active stimulation (n = 15)...

Neuron-targeted caveolin-1 overexpression attenuates cognitive loss and pathological transcriptome changes in symptomatic Alzheimer’s disease models

Thu, 19 Jun 2025 00:00:00 +0000

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by progressive synaptic loss and cognitive decline. Gene therapy that augments intrinsic neuroprotective pathways offers a promising strategy to mitigate neurodegeneration and prevent further cognitive loss. Caveolin-1 (Cav-1), a membrane lipid raft (MLR) scaffolding protein, regulates multiple pro-growth and pro-survival signaling pathways within plasmalemmal microdomains. Previously, we showed that AAV9-Synapsin-promoted Cav-1 (SynCav1) delivered to presymptomatic AD mice preserved cognitive functions and MLR-associated neurotrophic signaling. However, the therapeutic potential of SynCav1 delivered at the symptomatic stage of AD had not been tested. Therefore, the current study investigated the effect of hippocampal SynCav1 delivery at symptomatic age in two distinct preclinical AD models of amyloid pathology: PSAPP and APPKI mice. Our results demonstrated that SynCav1 delivery to PSAPP and APPKI...

Cryoneurolysis: Major Problems Rarely Discussed (or “Don’t Be Fooled—The Ice Ball Lies!”)

Thu, 5 Jun 2025 00:00:00 +0000

Cryoneurolysis: Major Problems Rarely Discussed (or “Don’t Be Fooled—The Ice Ball Lies!”)

Ultrasound Neuromodulation (Low‐Intensity Focused Ultrasound) to Treat Knee Osteoarthritis Pain

Thu, 5 Jun 2025 00:00:00 +0000

Low-intensity focused ultrasound is a non-invasive neuromodulation technique that delivers mechanical forces to a deep location within the body through acoustic pressure waves without affecting tissue between the transducer and focal target. Preliminary studies involving healthy volunteers suggest focused ultrasound reversibly prevents action potential formation similar to a local anesthetic nerve block, but the modality has not been used in patients with existing pain. The current randomized pilot study was undertaken to 1) determine the feasibility and optimize the protocol for a subsequent definitive clinical trial; and 2) monitor for related complications of focused ultrasound when treating knee osteoarthritis pain.

Multidimensional Analysis of Twin Sets During an Intensive Week-Long Meditation Retreat: A Pilot Study

Thu, 5 Jun 2025 00:00:00 +0000

ObjectivesMeditation has long been known to promote health. We utilized a multidisciplinary approach to investigate the impact of mind–body interventions on the body in a twin cohort during a week-long meditation retreat.MethodThis study was designed to address individual changes controlling for intersubject trait variation and explore the role of genetic background on multi-omic factors during meditation. Transcriptomic analysis was carried out from whole blood samples, while metabolomic and biochemical studies were carried out in blood plasma. Quantitative electroencephalography studies, coupled with biometric analysis and molecular studies at multiple time points, were carried out in twins meditating together and in twins separated and simultaneously either meditating or listening to a documentary.ResultsChanges in gene expression, metabolites, and cytokines in blood plasma associated with specific meditative states showed patterns of change relative to the time point being...

A Novel Percutaneous Device Enabling both Local Anesthetic Delivery and Electrical Stimulation (Neuromodulation) of Peripheral Nerves for Pain Following Orthopaedic Surgery: An Initial Feasibility Technical Report

Thu, 5 Jun 2025 00:00:00 +0000

Introduction: Pain following orthopaedic surgical procedures remains undertreated due to inadequate analgesic options. One possible solution is a novel device currently under investigation. The RELAY system (Gate Science, Moultonborough, NH) is comprised of a basic catheter-over-needle device to allow ultrasound-guided percutaneous insertion, leaving a perineural catheter after simple withdrawal of the internal needle. A single-injection bolus of local anesthetic may be quickly administered. Following surgery, the catheter may be attached to a portable infusion pump to provide an ambulatory continuous peripheral nerve block. Unlike previously described perineural catheters, the RELAY has an embedded wire and integrated pulse generator that permit stimulation of the targeted peripheral nerve(s) for up to 28 days. We here provide the first description of this novel device when used to provide postoperative analgesia. Case Report: A 67-year-old woman undergoing unilateral...

Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use

Thu, 8 May 2025 00:00:00 +0000

Posttraumatic stress disorder (PTSD) is associated with poor hippocampal function and disrupted pattern recognition. Cannabis use is highly prevalent in individuals with PTSD, yet the impact on these cognitive functions is poorly understood. Participants (n = 111) with a range of PTSD symptoms with and without regular cannabis use completed the mnemonic similarity task. We hypothesized that regular use would be associated with alterations in pattern separation ability in individuals with PTSD symptoms. High PTSD symptoms were associated with reduced pattern separation performance in minimal users. Regular users with high PTSD symptoms showed greater pattern separation, but reduced pattern separation with low PTSD symptoms. These results suggest that regular cannabis use may disrupt pattern separation and similar hippocampal-dependent processes, while it may improve pattern separation in individuals with high PTSD symptoms. These cross-sectional results require longitudinal follow-up...

National trends in perioperative epidural analgesia use for surgical patients

Mon, 21 Apr 2025 00:00:00 +0000

STUDY OBJECTIVE: Newer regional anesthesia techniques and minimally invasive surgeries have yielded decreased postoperative pain scores, potentially leading to decreased need for perioperative epidural analgesia. Limited literature is available on trends in usage rates of epidurals. The objective of this study was to identify trends in perioperative epidural analgesia rates among multiple fields of surgery. METHODS: All patients undergoing general, thoracic, urologic, plastic, vascular, orthopedic, or gynecological surgery in 2014-2020 were included from the National Surgical Quality Improvement Program database of over 700 hospitals in the U.S. and 11 different countries. Annual trends in epidural analgesia for all surgeries and each surgical specialty were assessed by mixed effects multivariable logistic regression. The odds ratios (OR) and 99 % confidence intervals (CI) were reported. RESULTS: There were 3,111,435 patients from 2014 to 2020 that were included in the final...

Role of TLR4 activation and signaling in bone remodeling, and afferent sprouting in serum transfer arthritis

Mon, 21 Apr 2025 00:00:00 +0000

BackgroundIn the murine K/BxN serum transfer rheumatoid arthritis (RA) model, tactile allodynia persists after resolution of inflammation in male and partially in female wild type (WT) mice, which is absent in Toll-like receptor (TLR)4 deficient animals. We assessed the role of TLR4 on allodynia, bone remodeling and afferent sprouting in this model of arthritis.MethodsK/BxN sera were injected into male and female mice with conditional or stable TLR4 deletion and controls. Paw swelling was scored and allodynia assessed by von Frey filaments. At day 28, synovial neural fibers were visualized with confocal microscopy and bone density assayed with microCT. Microglial activity and TLR4 dimerization in spinal cords were examined by immunofluorescence and flow cytometry.ResultsIn the synovium, K/BxN injected WT male and female mice showed robust increases in calcitonin gene related-peptide (CGRP+), tyrosine hydroxylase (TH)+ and GAP43+ nerve fibers. Trabecular bone density by microCT...

A perspective: neuraxial therapeutics in pain management: now and future

Mon, 21 Apr 2025 00:00:00 +0000

The neuraxial delivery of drugs for the management of pain and other spinal pathologies is widely employed and is the subject of a large volume of ongoing research with several thousand papers appearing in the past 5 years alone on neuraxial delivery. Several learned texts have been recently published. A number of considerations have contributed to this widespread interest in the development of the use of neuraxial therapeutics to manage pain. In the following section, major topics relevant to spinal encoding and in the use of neuraxial therapeutics are considered by the Frontiers in Pain Research editors of the research topic: "Neuraxial Therapeutics in Pain Management: Now and Future". This paper seeks to serve as a perspective to encourage the submission of manuscripts reflecting research in this exciting area.

Virally-initiated pain states: phenotypes, mechanisms, and future directions

Mon, 21 Apr 2025 00:00:00 +0000

The recent SARS-CoV-2 pandemic has underscored the significance of viral infections, affecting billions of lives and costing trillions of dollars globally. Even beyond SARS-CoV-2, common infections with viruses like influenza, HIV, and herpesviruses have profound impacts beyond their typical manifestations, often triggering acute and chronic pain syndromes that can be life-altering. These virally induced pain states can arise through direct viral replication within neurons, or indirectly, via immune responses to infection in both the contexts of afferent signaling in the dorsal root ganglion (DRG) or subsequent higher order integration in intracranial systems. Varicella-zoster virus (VZV), influenza virus, and SARS-CoV-2 each provide a unique lens through which to examine the interplay between viral activity and pain. This perspective paper is not meant to be an exhaustive review of virally-induced neuropathic pain states. It seeks to explore curated aspects of the complexities...

Classifying High-Risk Patients for Persistent Opioid Use After Major Spine Surgery: A Machine-Learning Approach

Sat, 19 Apr 2025 00:00:00 +0000

BACKGROUND: Persistent opioid use is a common occurrence after surgery and prolonged exposure to opioids may result in escalation and dependence. The objective of this study was to develop machine-learning-based predictive models for persistent opioid use after major spine surgery. METHODS: Five classification models were evaluated to predict persistent opioid use: logistic regression, random forest, neural network, balanced random forest, and balanced bagging. Synthetic Minority Oversampling Technique was used to improve class balance. The primary outcome was persistent opioid use, defined as patient reporting to use opioids after 3 months postoperatively. The data were split into a training and test set. Performance metrics were evaluated on the test set and included the F1 score and the area under the receiver operating characteristics curve (AUC). Feature importance was ranked based on SHapley Additive exPlanations (SHAP). RESULTS: After exclusion (patients with missing follow-up...

Intraarticular monomethyl fumarate as a perspective therapy for osteoarthritis by macrophage polarization