MuscleMap: An Open-Source, Community-Supported Consortium for Whole-Body Quantitative MRI of Muscle.

Disorders affecting the neurological and musculoskeletal systems represent international health priorities. A significant impediment to progress in trials of new therapies is the absence of responsive, objective, and valid outcome measures sensitive to early disease changes. A key finding in individuals with neuromuscular and musculoskeletal disorders is the compositional changes to muscles, evinced by the expression of fatty infiltrates.

A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury.

Chronic primary pain conditions (CPPCs) affect over 100 million Americans, predominantly women. They remain ineffectively treated, in large part because of a lack of valid animal models with translational relevance. Here, we characterized a CPPC mouse model that integrated clinically relevant genetic (catechol-O-methyltransferase; COMT knockdown) and environmental (stress and injury) factors.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery.

Role of Blood-Brain Barrier Dysfunction in Delirium following Non-cardiac Surgery in Older Adults.

Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.

Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Postoperative pain is a major clinical problem imposing a significant burden on our patients and society. Up to 57% of patients experience persistent postoperative pain 2 years after orthopedic surgery [49]. Although many studies have contributed to the neurobiological foundation of surgery-induced pain sensitization, we still lack safe and effective therapies to prevent the onset of persistent postoperative pain.

A Role for Blood-brain Barrier Dysfunction in Delirium following Non-Cardiac Surgery in Older adults.

Objective: Although animal models suggest a role for blood-brain barrier dysfunction in postoperative delirium-like behavior, its role in postoperative delirium and postoperative recovery in humans is unclear. Thus, we evaluated the role of blood-brain barrier dysfunction in postoperative delirium and hospital length of stay among older surgery patients.

Methods: Cognitive testing, delirium assessment, and cerebrospinal fluid and blood sampling were prospectively performed before and after non-cardiac, non-neurologic surgery.

Transforming Growth Factor-β-Activated Kinase 1 (TAK1) Mediates Chronic Pain and Cytokine Production in Mouse Models of Inflammatory, Neuropathic, and Primary Pain.

The origin of chronic pain is linked to inflammation, characterized by increased levels of proinflammatory cytokines in local tissues and systemic circulation. Transforming growth factor beta-activated kinase 1 (TAK1) is a key regulator of proinflammatory cytokine signaling that has been well characterized in the context of cancer and autoimmune disorders, yet its role in chronic pain is less clear. Here, we evaluated the ability of our TAK1 small-molecule inhibitor, takinib, to attenuate pain and inflammation in preclinical models of inflammatory, neuropathic, and primary pain.

Sensory Neuron-TRPV4 Modulates Temporomandibular Disorder Pain Via CGRP in Mice.

Temporomandibular disorder (TMD) pain that involves inflammation and injury in the temporomandibular joint (TMJ) and/or masticatory muscle is the most common form of orofacial pain. We recently found that transient receptor potential vanilloid-4 (TRPV4) in trigeminal ganglion (TG) neurons is upregulated after TMJ inflammation, and TRPV4 coexpresses with calcitonin gene-related peptide (CGRP) in TMJ-innervating TG neurons. Here, we extended these findings to determine the specific contribution of TRPV4 in TG neurons to TMD pain, and examine whether sensory neuron-TRPV4 modulates TMD pain via CGRP.

Rationale and design of a multicenter randomized clinical trial of vestibulodynia: understanding pathophysiology and determining appropriate treatments (vestibulodynia: UPDATe).

Background: Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.

Complementary Approaches for Military Women with Chronic Pelvic Pain: A Randomized Trial.

Active duty (AD) women suffer with chronic pelvic pain (CPP) while providers tackle diagnoses and treatments to keep them functional without contributing to the opioid epidemic. The purpose of this randomized trial was to determine the effectiveness of noninvasive, self-explanatory mindfulness-based stress reduction (MBSR) or self-paced healthy lifestyle (HL) interventions on CPP in AD women. A 6-week, interventional prospective study with AD women aged 21-55 years at Mountain Home (MTHM), Idaho, was conducted.

Expression of ectopic heat shock protein 90 in male and female primary afferent nociceptors regulates inflammatory pain.

Heat shock protein 90 (Hsp90) is a ubiquitously expressed integral cellular protein essential for regulating proteomic stress. Previous research has shown that Hsp90 regulates critical signaling pathways underlying chronic pain and inflammation. Recent discovery of membrane bound ectopic Hsp90 (eHsp90) on tumor cells has shown that Hsp90 induction to the plasma membrane can stabilize disease-relevant proteins.

IL-23 Enhances C-Fiber-Mediated and Blue Light-Induced Spontaneous Pain in Female Mice.

The incidence of chronic pain is especially high in women, but the underlying mechanisms remain poorly understood. Interleukin-23 (IL-23) is a pro-inflammatory cytokine and contributes to inflammatory diseases (e.g.

A genetic polymorphism that is associated with mitochondrial energy metabolism increases risk of fibromyalgia.

Alterations in cellular energy metabolism have been implicated in chronic pain, suggesting a role for mitochondrial DNA. Previous studies reported associations of a limited number of mitochondrial DNA polymorphisms with specific pain conditions. In this study, we examined the full mitochondrial genomes of people with a variety of chronic pain conditions.

Low catechol-O-methyltransferase and stress potentiate functional pain and depressive behavior, especially in female mice.

Low levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, and stress, which potentiates catecholamine release from sympathetic nerves, are fundamental to chronic functional pain syndromes and comorbid depression, which predominantly affect females. Here, we sought to examine the independent and joint contributions of low COMT and stress to chronic functional pain and depression at the behavioral and molecular level. Male and female C57BL/6 mice received sustained systemic delivery of the COMT inhibitor OR486 over 14 days and underwent a swim stress paradigm on days 8 to 10.

Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males.

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study.

A moldable sustained release bupivacaine formulation for tailored treatment of postoperative dental pain.

A moldable and biodegradable dental material was designed for customized placement and sustained delivery of bupivacaine (BP) within an extraction cavity. Microparticles comprising poly(lactic-co-glycolic acid) (PLGA) containing BP were generated via solvent-evaporation and combined with absorbable hemostat Gelfoam®. Kinetics of drug release were evaluated by in vitro dialysis assays, showing higher release within the first 24 hours, with subsequent tapering of release kinetics.

Acupuncture Resolves Persistent Pain and Neuroinflammation in a Mouse Model of Chronic Overlapping Pain Conditions.

Patients with chronic overlapping pain conditions have decreased levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Consistent with clinical syndromes, we previously demonstrated that COMT inhibition in rodents produces persistent pain and heightened immune responses. Here, we sought to determine the efficacy of manual acupuncture in resolving persistent pain and neuroinflammation in the classic inbred C57BL/6 strain and the rapid-wound healing MRL/MpJ strain.

Sustained stimulation of β- and β-adrenergic receptors leads to persistent functional pain and neuroinflammation.

Functional pain syndromes, such as fibromyalgia and temporomandibular disorder, are associated with enhanced catecholamine tone and decreased levels of catechol-O-methyltransferase (COMT; an enzyme that metabolizes catecholamines). Consistent with clinical syndromes, our lab has shown that sustained 14-day delivery of the COMT inhibitor OR486 in rodents results in pain at multiple body sites and pain-related volitional behaviors. The onset of COMT-dependent functional pain is mediated by peripheral β- and β-adrenergic receptors (β- and βARs) through the release of the pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6).

Epiregulin and EGFR interactions are involved in pain processing.

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing.

Incidence and Risk Factors for Pelvic Pain After Mesh Implant Surgery for the Treatment of Pelvic Floor Disorders.

Study Objective: Our aim was to assess incidence and risk factors for pelvic pain after pelvic mesh implantation.

Design: Retrospective study (Canadian Task Force classification II-2).

Setting: Single university hospital.

Circulating Omentin-1 and Chronic Painful Temporomandibular Disorders.

Aims: To investigate the relationship between omentin-1 levels and painful temporomandibular disorders (TMD).

Methods: In a case-control design, chronic painful TMD cases (n = 90) and TMD-free controls (n = 54) were selected from participants in the multisite OPPERA study (Orofacial Pain: Prospective Evaluation and Risk Assessment). Painful TMD case status was determined by examination using established Research Diagnostic Criteria for TMD (RDC/TMD).

Novel intrathecal and subcutaneous catheter delivery systems in the mouse.

Background: Catheter systems that permit targeted delivery of genes, molecules, ligands, and other agents represent an investigative tool critical to the development of clinically relevant animal models that facilitate the study of neurological health and disease. The development of new sustained catheter delivery systems to spinal and peripheral sites will reduce the need for repeated injections, while ensuring constant levels of drug in plasma and tissues.

New Method: Here, we introduce two novel catheter delivery systems in the mouse: the O'Buckley intrathecal catheter system for sustained delivery to the spinal region and a subcutaneous bifurcated catheter system for sustained drug delivery to both hindpaws.