In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer's Disease Models.

Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields (QY), relatively long emission wavelengths, and high signal-to-noise ratios (SNRs) to fulfill the requirements for 3D brain imaging in vivo.

Pain sensitivity differs between dog breeds but not in the way veterinarians believe.

Background: Veterinarians hold distinct breed-specific pain sensitivity beliefs that differ from the general public but are highly consistent with one another. This is remarkable as there is no current scientific evidence for biological differences in pain sensitivity across dog breeds. Therefore, the present study evaluated whether pain sensitivity thresholds differ across a set of dog breeds and, if so, whether veterinarians' pain sensitivity ratings explain these differences or whether these ratings are attributed to behavioral characteristics.

Acute radiotherapy-associated oral pain may promote tumor growth at distant sites.

Introduction: Patients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression.

Influence of exercise on pain is associated with resting-state functional connections: A cross-sectional functional brain imaging study.

Exercise is associated with lower prevalence and severity of pain, and is widely recommended for pain management. However, the mechanisms the exercise effect on pain remain unclear. In this study, we examined the association of exercise with pain and aimed to identify its neurobiological mediators.

Morphometric similarity networks discriminate patients with lumbar disc herniation from healthy controls and predict pain intensity.

We used a recently advanced technique, morphometric similarity (MS), in a large sample of lumbar disc herniation patients with chronic pain (LDH-CP) to examine morphometric features derived from multimodal MRI data. To do so, we evenly allocated 136 LDH-CPs to exploratory and validation groups with matched healthy controls (HC), randomly chosen from the pool of 157 HCs. We developed three MS-based models to discriminate LDH-CPs from HCs and to predict the pain intensity of LDH-CPs.

Activity patterns are associated with fractional lifespan, memory, and gait speed in aged dogs.

Maintaining an active lifestyle is considered a hallmark of successful aging. Physical activity significantly reduces the risk of cognitive decline and Alzheimer's disease in humans. However, pain and lack of motivation are important barriers to exercise.

Minimal clinically-important differences for the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) client-reported outcomes measures.

Client-reported outcomes measures (CROMs) have been previously validated for the evaluation of canine osteoarthritis. A published systematic review indicated that the 'Liverpool Osteoarthritis in Dogs' (LOAD) and the 'Canine Orthopedic Index' (COI) can be recommended for use in dogs with osteoarthritis; these CROMs have also been used in the context of measuring surgical outcomes of dogs with orthopaedic conditions. However, the minimal clinically-important differences (MCIDs) for these CROMs have not been investigated.

Role of 5-HT1A-mediated upregulation of brain indoleamine 2,3 dioxygenase 1 in the reduced antidepressant and antihyperalgesic effects of fluoxetine during maintenance treatment.

The reduced antidepressant and antihyperalgesic effects of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine during maintenance treatment has been reported, but little is known about the molecular mechanism of this phenomenon. In three comorbid pain and depression animal models (genetic predisposition, chronic social stress, arthritis), we showed that the fluoxetine's antidepressant and antihyperalgesic effects were reduced during the maintenance treatment. Fluoxetine exposure induced upregulation of the 5-hydroxytryptamine 1A (5-HT1A) auto-receptor and indoleamine 2,3 dioxygenase 1 (IDO1, a rate-limiting enzyme of tryptophan metabolism) in the brainstem dorsal raphe nucleus (DRN), which shifted the tryptophan metabolism away from the 5-HT biosynthesis.

Predicting placebo analgesia in patients with chronic pain using natural language processing: a preliminary validation study.

Patients with chronic pain show large placebo effects in clinical trials, and inert pills can lead to clinically meaningful analgesia that can last from days to weeks. Whether the placebo response can be predicted reliably, and how to best predict it, is still unknown. We have shown previously that placebo responders can be identified through the language content of patients because they speak about their life, and their pain, after a placebo treatment.

Structural brain connectivity predicts early acute pain after mild traumatic brain injury.

Mild traumatic brain injury (mTBI), is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute postinjury pain is important because it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 157 patients with mTBI, following a motorized vehicle collision.

Initial exploration of the discriminatory ability of the PetPace collar to detect differences in activity and physiological variables between healthy and osteoarthritic dogs.

Background: Accelerometry has been used to evaluate activity in dogs with osteoarthritis (OA) pain, especially in relation to effect of treatment; however no studies have compared accelerometry-measured activity in dogs with OA-pain and healthy dogs. The aims of this study were to (1) compare activity output from the PetPace collar with the validated Actical monitor and (2) determine if PetPace collar outputs (overall activity, activity levels, body position, and vital signs) differed between healthy dogs and dogs with OA-pain.

Methods: This was an observational, non-interventional study in healthy dogs and dogs with OA-pain.

The beneficial role of companion animals in translational pain research.

The use of spontaneous painful disease in companion pet animals has been highlighted as one of the changes that could be made to help improve translation of basic science to new therapeutics, acting as a bridge between preclinical and clinical studies, with the goal of accelerating the approval of new therapeutics. This review focuses on the utility of companion pet dogs for translational research by reviewing what outcome measures can be measured, and importantly, the relevance of these outcome measures to human translational research. It also details the practical considerations involved in incorporating companion dogs into human therapeutic development.

Static posturography as a novel measure of the effects of aging on postural control in dogs.

Aging is associated with impairment in postural control in humans. While dogs are a powerful model for the study of aging, the associations between age and postural control in this species have not yet been elucidated. The aims of this work were to establish a reliable protocol to measure center of pressure excursions in standing dogs and to determine age-related changes in postural sway.

Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is an underrecognized public health threat. Survivors of TBI often suffer long-term neurocognitive deficits leading to the progressive onset of neurodegenerative disease. Recent data suggests that the gut-brain axis is complicit in this process.

A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain.

Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity.

Trend analysis of drug overdose deaths before and during the COVID-19 pandemic.

Data from a single state indicated there was an increase in opioid overdose related emergency services during the COVID-19 pandemic. The current study examined the provisional rolling 12-month drug overdose deaths between January 2019 and October 2021 at the national, state, and specific-drug levels, to identify trends in drug-overdose deaths before and during the COVID-19 pandemic. The trend in provisional U.

Gut Microbiome in Anesthesiology and Pain Medicine.

The gut microbiome plays critical roles in human health and disease. Recent studies suggest it may also be associated with chronic pain and postoperative pain outcomes. In animal models, the composition of the gut microbiome changes after general anesthesia and affects the host response to medications, including anesthetics and opioids.

On the Relationship Between Pain Variability and Relief in Randomized Clinical Trials.

Previous research reports suggest greater baseline variability is associated with greater pain relief in those who receive a placebo. However, studies that evidence this association do not control for confounding effects from regression to the mean and natural history. In this report, we analyzed data from two randomized clinical trials (Placebo I and Placebo II, total = 139) while adjusting for the effects of natural history and regression to the mean a no treatment group.

What Is the Numerical Nature of Pain Relief?

Pain relief, or a decrease in self-reported pain intensity, is frequently the primary outcome of pain clinical trials. Investigators commonly report pain relief in one of two ways: using raw units (additive) or using percentage units (multiplicative). However, additive and multiplicative scales have different assumptions and are incompatible with one another.

Intensity of perioperative analgesia but not pre-treatment pain is predictive of survival in dogs undergoing amputation plus chemotherapy for extremity osteosarcoma.

The purpose of this bi-institutional retrospective study was to determine whether, in dogs treated with limb amputation and adjunctive chemotherapy for osteosarcoma, oncologic outcomes are impacted by either: (1) baseline cancer pain severity, or (2) the approaches used for perioperative pain management. Data were extracted from the medical records of 284 dogs that underwent both limb amputation and chemotherapy (carboplatin and/or doxorubicin) between 1997 and 2017 for localized (non-metastatic) osteosarcoma of the appendicular skeleton. Kaplan-Meier survival curves and Cox proportional hazard (PH) models were used to determine the impact that retrospectively scored baseline pain levels (high vs.

Limits of decoding mental states with fMRI.

A growing number of studies claim to decode mental states using multi-voxel decoders of brain activity. It has been proposed that the fixed, fine-grained, multi-voxel patterns in these decoders are necessary for discriminating between and identifying mental states. Here, we present evidence that the efficacy of these decoders might be overstated.

TrpNet: Understanding Tryptophan Metabolism across Gut Microbiome.

Crosstalk between the gut microbiome and the host plays an important role in animal development and health. Small compounds are key mediators in this host-gut microbiome dialogue. For instance, tryptophan metabolites, generated by biotransformation of tryptophan through complex host-microbiome co-metabolism can trigger immune, metabolic, and neuronal effects at local and distant sites.