Crossover Study Research Articles

Unraveling the contribution of melamine tableware for human internal exposure to melamine and its derivatives: Insights from crossover and biomonitoring studies

Melamine tableware can release melamine in daily-use; however, currently there is insufficient evidence to support whether the amount released could pose human exposure risk. We therefore conducted two studies, one is 8-day randomized crossover trial involving 27 volunteers who used melamine and stainless-steel tableware in turn (n = 648) and the other is cross-sectional study including 113 college students and 200 residents (n = 313) to further provide population-based evidence. The crossover study results showed that using melamine tableware could promote urinary concentrations of melamine, cyanuric acid (CYA), and ammelide by 42.1 %, 66.9 %, and 36.2 %, respectively. In the biomonitoring survey, students who are more accessible to melamine tableware in the canteen had 1.47-fold higher median urinary concentrations of melamine-related compounds than that of common residents (393 vs 267 nmol/L, p < 0.01). Additionally, positive associations between exposure to melamine and an oxidative stress indicator, 8-oxo-7,8-dihydroguanine (β = 1.13, 95 % CI: 0.32, 1.94), and CYA and 8-hydroxy-2′-deoxyguanosine (β = 0.87, 95 % CI: 0.22, 1.53) were observed in students (p < 0.01), indicating long-term chronic exposure to these chemicals may induce molecular damage to nucleic acids. Our findings provide compelling evidence that frequent use of melamine tableware continues to be a potential threat to human health.

The glucagon-like peptide-1 and other endocrine responses to alcohol ingestion in women with versus without metabolic surgery.

Glucagon-like peptide-1 (GLP-1)-based therapies, effective in treating obesity and type 2 diabetes, hold potential for reducing alcohol-seeking behaviour. However, the understanding of how alcohol consumption affects endogenous GLP-1 responses-important for understanding GLP-1-based therapies' potential in addressing alcohol misuse-is limited, given the absence of placebo-controlled studies examining these effects. This study aimed to determine the acute effects of alcohol ingestion on GLP-1 and other peptides and evaluate whether metabolic surgery, which increases GLP-1 responses, blood alcohol concentrations (BAC) and alcohol misuse risk, influences this effect. Additionally, we assessed the acute effects of alcohol on plasma glucose and insulin concentrations. Using a placebo-controlled crossover study, we examined hormonal and glucose responses after oral alcohol consumption (0.5g/kg of fat-free mass) versus placebo drinks in 18 women who underwent metabolic surgery <5years ago and in 14 non-operated controls (equivalent in age, body mass index [BMI], race and alcohol consumption patterns). Women had a mean (SD) age of 41 (10) years and a BMI of 33 (5) kg/m2. Compared with the control group, the surgery group exhibited a higher peak BAC (0.99 [0.20] g/L vs. 0.75 [0.16] g/L; P < 0.005). Alcohol decreased GLP-1 by 34% (95% CI, 16%-52%) in both groups and decreased ghrelin more in the control (27%) than in the surgery group (13%). Alcohol modestly decreased plasma glucose and transiently increased insulin secretion in both groups (P < 0.05). However, alcohol lowered blood glucose concentrations to the hypoglycaemic range in 28% of the women in the surgery group versus none in the control group. These findings provide compelling evidence that acute alcohol consumption decreases GLP-1, a satiation signal, elucidating alcohol's 'apéritif' effect. This study also highlights the potential increase in alcohol-related hypoglycaemic effects after metabolic surgery.

Pain during and after different swim strokes in chronic low back pain: a crossover study design

Pain during and after different swim strokes in chronic low back pain: a crossover study design

Protein-based oral rehydration solutions for patients with an ileostomy: A randomised, double-blinded crossover study

Protein-based oral rehydration solutions for patients with an ileostomy: A randomised, double-blinded crossover study

Absolute oral bioavailability of milvexian spray-dried dispersion formulation under fasted and fed conditions in healthy adult participants: An intravenous microtracer approach.

Milvexian is an oral, small-molecule factor XIa inhibitor being developed to prevent thromboembolic events. This study assessed the absolute bioavailability (F) of milvexian following single doses of milvexian spray-dried dispersion (SDD) formulation under fed and fasted conditions, and milvexian solution, in healthy adult participants using an intravenous microtracer approach. This was a phase I, open-label, partially randomized, 4-sequence, 5-period crossover study. After fasting for ≥10 h, participants received milvexian 200-mg oral solution with a 100-μg 14C milvexian intravenous microtracer at the time of maximum observed plasma concentration. Following a 3-day washout, participants were randomized to 1 of 4 milvexian SDD treatment sequences in a crossover fashion: 25 mg fasted, 25 mg fed, 200 mg fasted, or 200 mg fed. Pharmacokinetic data were collected up to 72 h postdose. Seventeen participants were dosed, and 14 completed treatment. Under fasted conditions, milvexian F was ~100%, 58.2%, and 54.2% following administration of the oral solution, 25 mg SDD, and 200 mg SDD, respectively. Under fed conditions, milvexian F following 25 mg and 200 mg SDD was 44.3% and 75.6%, respectively. The milvexian SDD formulation at 25 mg and 200 mg resulted in similar F in a fasted state; under fed conditions, milvexian F decreased at 25 mg and increased at 200 mg. These findings clarify pharmacokinetic-related gaps observed in previous studies.

Cerebral and myocardial kinetics of [11C]acetoacetate and [11C]β-hydroxybutyrate: A comparative crossover study in healthy rats

BackgroundKetone metabolism has been studied using positron emission tomography (PET) with the radiotracers [11C]acetoacetate and [11C]β-hydroxybutyrate. However, whether these two radiotracers actually yield equivalent estimates of cerebral and myocardial ketone metabolism has not yet been investigated. This study aimed to investigate and compare the kinetics of both tracers in the brain and heart of healthy rats under varying levels of circulating ketones at baseline and after a single-dose exogenous ketone ester (KE) supplement. MethodsSix healthy Sprague-Dawley rats each underwent two scans with each tracer: one following oral KE administration and one with a placebo. Cerebral kinetic parameters (Ki, VT, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (K1, k2, and VT) were derived using a 1-tissue compartment model. Parameters were compared through mixed-effects, correlation, and Bland-Altman analyses. ResultsGlobal CMR increased 3–4-fold in the KE group versus placebo, with strong positive correlations between CMR and plasma ketone levels for both tracers. Correlations between [11C]acetoacetate and [11C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as Ki (ρ = 0.40) and for VT (ρ = 0.38) but strongly positive for absolute uptake, CMR (r = 0.84), with a non-significant mean bias of −0.03. In contrast, myocardial kinetics showed only non-significant weak to moderate correlations between the radiotracers (K1 (r = 0.04), k2 (r = −0.27), and VT (ρ = 0.43)), with no systematic biases. Conclusion[11C]acetoacetate and [11C]β-hydroxybutyrate can be used interchangeably for measuring global CMR in healthy rats but differ in certain cerebral and myocardial kinetics. Whether these findings are generalizable to pathological conditions warrants further studies to explore the kinetics of these tracers in disease models.

Effects of oral capromorelin on food intake and body weight in healthy, four-toed hedgehogs (Atelerix albiventris)

Background: Although inappetence is a common clinical sign in ill four-toed hedgehogs (Atelerix albiventris), there is limited information on the use of appetite stimulants in this species. Capromorelin is a growth hormone secretagogue that acts as a selective ghrelin receptor agonist. It has been demonstrated to increase food intake in dogs and cats with normal appetite as well as in dogs with inappetence. Methods: The effects of capromorelin on food intake and body weight were studied in a randomized, blinded, placebo-controlled, complete cross-over study in 10 healthy adult hedgehogs. Baseline food intake and body weight were recorded, and hedgehogs were administered either capromorelin (10 mg/kg) or an equivalent volume (0.33 mL/kg) of an oral compounding vehicle PO via syringe daily in the early evening for 5 days. Food intake and body weight were measured daily for 4 days following the last dose. Results: Hedgehogs produced foamy saliva during oral administration regardless of treatment. Over the 5-day treatment period, hedgehogs administered capromorelin ate more food (median: 11%, range: -37 to 71%) than hedgehogs in the control group, and 7/10 (70%) hedgehogs administered capromorelin had an increase in food intake. However, this change in food intake was not statistically significantly different when compared to the control group. Body weight did not increase following capromorelin administration. Conclusions and Clinical Relevance: Unlike in other species, repeated daily oral administration of capromorelin doses at 10 mg/kg does not appear to induce the same degree of appetite stimulation in hedgehogs. Further research is needed to determine if capromorelin is effective in hedgehogs with inappetence.

Rationale and design of OPT-RATE AF: A randomized clinical trial of increased physiologic pacing rates in heart failure with preserved ejection fraction

Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. OPT-RATE AF is a prospective, randomized crossover study of patients with HFpEF following AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats-per-minute (bpm) for 3 months and then switched to a rate of 80 bpm for 3 months, and vice versa. The primary endpoint is change in exercise capacity assessed by the 6-minute walk test. Notable secondary outcomes will include change in Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. EKG, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF following AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving QoL and other important cardiovascular outcomes.

Improving lung function capacity in patients with chronotropic incompetence using closed loop stimulation: A randomized crossover study

BackgroundChronotropic incompetence (CI) severely limits exercise tolerance due to impaired heart rate responses. This study investigated whether pacemaker with closed-loop stimulation (DDD-CLS) pacing, which provides rate acceleration in response to exertion, could enhance lung function and cardiopulmonary capacity compared pacemaker without CLS pacing in patients with CI. MethodsThis randomized crossover trial included 32 patients with CI who were compared to each CLS and DDD pacing over 2 months. Spirometry was used to assess the forced vital capacity (FVC). Cycling-based cardiopulmonary exercise testing (CPET) measured peak oxygen uptake (peak VO2). ResultsDDD-CLS pacing yielded significantly higher FVC (2.2 ± 0.8 L) versus DDD pacing (2.0 ± 0.7 L), p = 0.036, a 3.2% improvement. Moreover, those in the DDD-CLS mode showed a significantly higher FEV1 of 1.8 ± 0.6 L compared to the DDD mode of 1.7 ± 0.5 L (p = 0.03). Compared with DDD pacing, DDD-CLS pacing also achieved superior peak VO2 (14.9 ± 4.0 vs 12.2 ± 3.7 mlO2/kg/min, p < 0.001) and peak heart rate (106.9 ± 9.7 vs 98.3 ± 19.8 bpm, p = 0.013). DDD-CLS and DDD pacing modes showed significant correlations between FVC and peak VO2 and between peak VO2 and peak heart rate during CPET. ConclusionsCompared with DDD mode, DDD-CLS pacing provided physiological chronotropic support to improve cardiopulmonary function during exertion, which enhanced lung capacity in patients with CI.

Pharmacokinetic and Pharmacodynamic Profile of Epinephrine Nasal Spray Versus Intramuscular Epinephrine Autoinjector in Healthy Adults

BackgroundStandard of care for anaphylaxis treatment is intramuscular (IM) epinephrine. An epinephrine nasal spray (ENS) is under development as an alternative form of administration. ObjectiveTo compare the pharmacokinetic (PK) and pharmacodynamic (PD) profile of 13.2 mg ENS with 0.3 mg IM epinephrine auto-injector. MethodsData from 4 open-label phase 1 crossover studies conducted in healthy adults were pooled to determine the PK and PD profile of a single 13.2 mg ENS dose delivered by 2 consecutive sprays of 6.6 mg each in opposite (n=224 doses) or the same nostril (n=75 doses) compared with the 0.3 mg IM auto-injector (n=215 doses). Each participant served as their own control. Blood samples and vital signs were collected pre-dose and at multiple intervals from 0-360 minutes post-dose. ResultsENS rapidly increased the plasma epinephrine concentration, with levels that were overall greater than IM auto-injector. Median (range) time to maximum plasma epinephrine concentration with ENS opposite nostrils, ENS same nostril, and IM auto-injector was 25.1 (1.3, 362.1), 20.1 (3.0, 120.2), and 20.0 (1.0, 121.3) minutes, respectively. The area under the plasma concentration–time curve for 0-360 minutes was significantly higher with ENS than the IM auto-injector (geometric mean ratio [90% CI]=155% [140%, 172%] with ENS opposite nostrils, 159% [138%, 182%] with ENS same nostril). The PD effects on heart rate and blood pressure were similar in pattern and magnitude among all 3 treatment groups. ConclusionsENS rapidly achieved plasma epinephrine levels greater and more sustained than the IM auto-injector and with a similar PD effect.

Digital Evaluation of a Novel Impression Technique Combining Conventional and Intraoral Scans For Recording Abused Soft Tissue for Complete Denture Construction. A Clinical Controlled Crossover Study

Digital Evaluation of a Novel Impression Technique Combining Conventional and Intraoral Scans For Recording Abused Soft Tissue for Complete Denture Construction. A Clinical Controlled Crossover Study

Psychological and physiological benefits of horticultural therapy for Chinese older adults

Background Gardening as a leisure activity has been shown to be potentially beneficial for older adults, this study aimed to assess the physiological and psychological impacts of a specific horticultural activity, watering indoor plants, compared with playing a computer game - the Klondike Solitaire Card Game. Methods This crossover study included 100 older adults recruited from a nursing care facility for older people in Shanghai, China. They were allocated to either engage in watering indoor plants (horticultural group) or playing a computer game (control group). For the inclusion criteria, screening for cognitive function was conducted to exclude those with severe cognitive impairments, thereby focusing on those capable of participating fully in the study activities. Brainwave activities, blood pressure, and psychological states were measured through pre- and post-test questionnaires to evaluate the physiological and psychological effects. Results The activity of watering indoor plants was associated with significant reductions in both systolic and diastolic blood pressure, in contrast to the computer game activity. Additionally, participants in the horticultural group showed increased brainwave mean values, indicating heightened relaxation and focus, while decreases were observed in the control group. The experimental group reported reduced anxiety scores, along with increased feelings of comfort and relaxation, and also exhibited significantly higher meditation levels, which indicates a profound mental relaxation effect. Conclusion Our findings suggest that engaging in indoor horticultural activities, such as watering houseplants for 10 minutes, can reduce mental and physical stress levels in older adults.

Comparing Virtual Reality and Traditional Training in Radiation Safety Practices Over Three Years Among Cardiologists and Scrub Nurses

PurposeThis study evaluated the effectiveness of virtual reality (VR) training versus traditional methods in enhancing radiation safety practices among cardiologists and scrub nurses. Developed by Virtual Medical Coaching, VR training simulates radiation safety scenarios in cardiac catheterization laboratories (Cath Labs). MethodsA three-year crossover study was conducted with 150 healthcare professionals (in this study, healthcare professionals are defined as cardiologists and scrub nurses who work in Cath Labs) at five urban hospitals. These professionals are key personnel in fluoroscopy-guided interventional procedures, where radiation safety is a critical concern.Participants, stratified by profession, were randomly assigned to initially receive either VR (virtual medical coaching) or traditional training, followed by a year-long washout period before switching training modalities. Primary outcomes measured changes in radiation exposure via dosimeters, whereas secondary outcomes assessed knowledge retention. ResultsVR training significantly reduced radiation exposure, resulting in a 30% greater decrease in radiation dose than traditional methods do. Cardiologists in Group A (VR training) experienced a mean reduction of 3.37 (p < 0.001), whereas scrub nurses experienced a mean reduction of 2.89 (p < 0.001). In contrast, participants in Group B (traditional training) exhibited a smaller reduction of 1.75 for cardiologists (p < 0.001) and 1.49 for scrub nurses (p < 0.001). The participants transitioning from traditional to VR training demonstrated enhanced retention and application of safety protocols, as reflected by improved knowledge and observed structured clinical examinations (OSCE) scores. The integration of VR into training notably improved procedural knowledge and skills without the risk of radiation exposure, making VR an effective tool for radiation safety education. ConclusionThis study highlights the superiority of VR training in reducing radiation exposure and enhancing practical skills among medical professionals. Virtual medical coaching’s specialized VR modules effectively simulate real-world scenarios, making them valuable components in radiation safety training. The findings advocate the integration of VR into medical education curricula to improve safety standards and training efficacy.

Frontal Cortical Activity during Care Farming Activities of Adults Using Electroencephalogram

The underlying therapeutic mechanisms of care farming activities have not been addressed using psychophysiological data. We aimed to understand frontal cortex activation in adults during care farming activities and to explore the psychophysiological effects. Using a randomized crossover study method, 20 adults (average age, 31.3 ± 9.8 years) participated in 10 care farming activities, (four gardening activities, three animal-mediated activities, and three off-farming activities) for 3 minutes each at an actual care farm. Electroencephalography (EEG) was performed during the activity, and emotional states were assessed using subjective emotional questionnaires after each activity. The EEG results revealed that alpha activity increased during gardening activities, such as organizing garden plots and planting plants. Spectral edge frequency 50, which predicts the degree of arousal, increased during interaction with dogs. The results of the subjective emotional questionnaire revealed that participants experienced positive emotions, such as vigor, comfort, naturalness, and relaxation, when participating in care farming activities compared with those while resting. Therefore, this study suggests that care farming activities can induce changes in the frontal cortex activation and positive emotional states in participants. This study elucidates the use of such activities to address mental health-related issues.

Exploring the Efficacy of a Dynamic Harness System on Gross Motor Development and Motivation for Infants With Down Syndrome: A Pilot Study.

To explore the benefits of a Partial Body Weight Support (PBWS) harness system within a play enriched environment on gross motor development and mastery motivation of infants with Down Syndrome (DS). A randomized crossover study with 17 pre-walking infants with DS in two conditions-play with or without the harness engaged-each for 3×/week over 3weeks with a 1-week washout. Assessments took place at baseline, crossover, and completion. Statistically and clinically significant changes were evident on the Gross Motor Function Measure-88; however, there were no significant changes in parent-reported mastery motivation. The combination of PBWS harness system support and high frequency-facilitated play within an enriched play environment positively affected gross motor development. The intervention did not impact mastery motivation skills, and the direct impact of the harness remains unclear.

Effects of High-intensity Continuous Ultrasound on Infrapatellar Fat Pad Stiffness and Gliding in Healthy Participants: A Randomized, Single-blind, Placebo-controlled Crossover Trial

ObjectiveUltrasound therapy effectively treats a joint range of motion limitation and pain originating from soft tissue in knee osteoarthritis (OA). Few interventional studies have focused on the infrapatellar fat pad (IFP), and the effects of high-intensity continuous ultrasound (HICUS) on IFP stiffness and gliding have not been investigated. Therefore, we aimed to determine the effects of HICUS on IFP stiffness and gliding. MethodsThis single-blind, randomized, controlled crossover study involved 24 healthy participants. The HICUS and placebo conditions were applied to the knee joint on 2 different days. HICUS was performed (1 MHz, 2.5 W/cm², duty cycle 100%, 5 min) using an ultrasound machine equipped with an applicator and adsorption-type fixed automatic rotation irradiation function. The main outcomes were IFP stiffness and gliding measured at 10 degrees and 120 degrees knee flexion. Gliding was measured as the difference between the patellar-tendon tibial angles at 10 degrees and 120 degrees knee flexion. Measurements were performed before (T1), immediately after (T2), and 15 min after (T3) treatment. ResultsTwo-way repeated measures analysis of variance showed a significant interaction of IFP stiffness at 10 degrees knee flexion; post-test results showed that HICUS decreased stiffness at T2 and T3. There was no significant difference at 120 degrees. A significant interaction of gliding was observed under the HICUS condition. Post-tests showed that HICUS significantly improved gliding at T2 and T3. ConclusionHICUS is a simple, safe intervention for improving IFP stiffness and gliding in healthy participants, with sustained effects. Further studies are needed to evaluate its efficacy in patients.

Changes in drug crystallinity in a commercial tacrolimus amorphous formulation result in variable pharmacokinetics

Tacrolimus capsules contain the drug as the amorphous form. It is well known that drug crystallinity is a risk factor for the performance of amorphous formulations. This study investigated the impact of varying levels of crystalline drug on the pharmacokinetics of tacrolimus following oral dosing of a 5 mg capsule under fasting conditions. Two treatments with percent crystallinity of 20% and 50% were achieved by exposing a marketed generic tacrolimus product to open dish storage conditions of 35 °C and 75% relative humidity (RH) for up to 20 days. Crystallinity was monitored with X-ray powder diffraction. Prograf®, the reference listed drug (RLD), an amorphous generic drug product, and generic drug products containing 20% and 50% crystalline tacrolimus were evaluated. All four treatments were administered to healthy participants in a randomized, single-dose, four-treatment, four-period, four-way crossover study. Blood sampling occurred over 24 h. The amorphous generic tacrolimus product was determined not to be bioequivalent to the RLD. The capsules containing both 20% and 50% crystalline tacrolimus also failed the bioequivalence recommendations when compared to the amorphous generic or to the RLD. Both levels of crystalline tacrolimus resulted in BE failure for both Cmax and AUC parameters. The impact of tacrolimus crystallization was greater for maximum blood concentration (Cmax) values relative to the area-under-the-curve (AUC) values. This study demonstrates that crystalline tacrolimus formed in a marketed generic product and these changes resulted in variable pharmacokinetics which could be of significant clinical concern.

Fully digital versus conventional workflow: Are removable complete overdentures equally good? A randomized crossover trial.

Implant-supported removable complete overdentures (IODs) are a common treatment in case of edentulism and malfunctioning of the conventional denture. Manufacturing IODs in a conventional way (C-IODs) is time-consuming, but in a digital workflow, this can be done in three sessions. Digitally produced IODs (3D-IODs) are also more advantageous than C-IODs because lost or broken 3D-IODs can be swiftly reproduced as the digital design is always available. To prove in a non-inferiority study, with a margin of 0.3 point per Oral Health Impact Profile-20 (OHIP-20) question, that IODs made according to a fully digital workflow (3D-IODs), function as good as C-IODs with respect to patient-reported outcome measures (PROMs). This randomized crossover study included 36 fully edentulous patients who showed extreme resorption of the maxillary alveolar process, making denture retention difficult. After a maxillary bone augmentation and the installation of 4-6 implants, each patient wore both types of IOD for 1 year each, with the order reversed in two subsets of patients. The 3D-IODs and C-IODs were fabricated in advance for both jaws (at least two mandibular implants were already present). The OHIP-20 survey was performed at baseline, after 1 year (before the IOD switch), and after 2 years to determine patient satisfaction scores using a visual analog scale (VAS). The general health status was assessed using the Short Form (SF-36) questionnaire. Regarding the PROMs, patients preferred the 3D-IOD: the improvement on the overall OHIP scale (0-4), expressed as a mean, was 0.26 points greater than for the C-IOD (p < 0.001). This applied also to the VAS scale (1-100) with an increase of 7.37 points (p < 0.001). Regarding the SF-36 scale, only for the item "emotional well-being," the 3D-IOD scored significantly better (p = 0.033). Compared with conventionally fabricated C-IODs, fully digitally produced 3D-IODs resulted in significantly higher OHIP-20 and satisfaction scores.

Analgesic effect of intrapocket anesthesia gel during scaling and root planing: A randomized crossover study

Analgesic effect of intrapocket anesthesia gel during scaling and root planing: A randomized crossover study

Lameness of horses is effectively ameliorated with a low volume of mepivacaine administered as a palmar digital nerve block.

To determine the effect of 1.5 mL 2% mepivacaine, 0.75 mL 2% mepivacaine, and a combination of 0.75 mL 2% mepivacaine with epinephrine (1:200,000 solution) administered over each palmar digital nerve (PDN) to 6 horses with naturally occurring lameness caused by digital pain. In a crossover study design, 6 horses with forefoot-related lameness were randomly assigned to 1 of 3 groups. Each group received, on different study days, a PDN block using 1.5 mL of 2% mepivacaine, 0.75 mL 2% mepivacaine, or 0.75 mL of a combination of 2% mepivacaine and epinephrine (1:200,000 solution) injected over each nerve. The horses' gait while trotting was analyzed with an inertial, sensor-based motion-analysis system immediately before treatment. The assigned treatment was then administered to the lame forelimb, after which the gait was reevaluated at 5-minute intervals for 15 minutes. All 3 treatments significantly reduced lameness scores at all gait evaluations, but the effect of treatment on the lameness score did not differ significantly among treatments. 0.75 mL of mepivacaine hydrochloric acid injected over each PDN was as effective as twice that volume in decreasing the lameness score of horses with digital pain. The 0.75-mL solution of mepivacaine/epinephrine injected over each nerve did not significantly improve the anesthetic effect of mepivacaine. For a palmar digital nerve block, a lower-than-commonly-recommended volume of 2% mepivacaine effectively ameliorates digital pain. This finding invites investigation as to whether administering a low volume of local anesthetic will more precisely localize pain.