Mary Barbe

Temple University | TU · Department of Anatomy and Cell Biology

Radiation-induced fibrosis (RIF) is a common side effect of cancer treatment, but can manifest into a devastating syndrome for which there is no preventive measure or cure. In rats who perform a repetitive work task, who left untreated develop signs and symptoms that resemble repetitive motion disorders in humans, we have shown that manual therapy...

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co‐exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in ra...

Introduction Manual therapy refers to a range of hands-on interventions used by various clinical professionals, such as osteopaths, osteopathic physicians, chiropractors, massage therapists, physiotherapists, and physical therapists, to treat patients experiencing pain. Objectives To present existing evidence of mechanisms and clinical effectivene...

Vagus nerve stimulation (VNS) is emerging as potential treatment for several chronic diseases, however, limited control of fiber activation to promote desired effects over side effects restricts clinical translation. Here we describe a new VNS method that relies on intermittent, interferential sinusoidal current stimulation (i ² CS) through implant...

Vagus nerve stimulation (VNS) is emerging as potential treatment for several chronic diseases, however, limited control of fiber activation to promote desired effects over side effects restricts clinical translation. Here we describe a new VNS method that relies on intermittent, interferential sinusoidal current stimulation (i²CS) through implanted...

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the...

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelv...

A role for substance P has been proposed in musculoskeletal fibrosis, with effects mediated through transforming growth factor beta (TGFβ). We examined the in vitro effects of substance P on proliferation, collagen secretion, and collagen deposition in rat primary dermal fibroblasts cultured in medium containing 10% fetal bovine serum, with or with...

Poor sleep is thought to enhance pain via increasing peripheral and/or central sensitization. Aerobic exercise, conversely, relives pain via reducing sensitization, among other mechanisms. This raises two clinical questions: (1) does poor sleep contribute to the transition from acute-to-persistent pain, and (2) can exercise protect against this tra...

The matricellular protein cell communication factor 2/connective tissue growth factor (CCN2/CTGF) is critical to development of neuromuscular fibrosis. Here, we tested whether anti-CCN2 antibody treatment will reduce established forepaw fibro-degenerative changes and improve function in a rat model of overuse injury. Adult female rats performed a h...

Extracellular histones, part of the protein group known as damage-associated molecular patterns (DAMPs), are released from damaged or dying cells and can instigate cellular toxicity. Within the context of chronic obstructive pulmonary disease (COPD), there is an observed abundance of extracellular histone H3.3, indicating potential pathogenic impli...

Dupuytren disease is a progressive, benign fibroproliferative disorder of the hands that can lead to debilitating hand contractures. Once symptomatic, treatment involves either surgical intervention, specifically fasciectomy or percutaneous needle aponeurotomy, or enzymatic degradation with clostridial collagenase. Currently, collagenase is the onl...

Very little is known about the physiological role of nicotinic receptors in canine bladders, although functional nicotinic receptors have been reported in bladders of many species. Utilizing in vitro methods, we evaluated nicotinic receptors mediating bladder function in dogs: Control (9 female and 11 male normal controls, 5 sham-operated), Decentr...

Roles of redox signaling in bladder function is still under investigation. We explored the physiological role of reactive oxygen species (ROS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in regulating bladder function in humans and dogs. Mucosa-denuded bladder smooth muscle strips obtained from 7 human organ donors and 4 n...

Loss of function in transport protein particles (TRAPP) links a new set of emerging genetic disorders called “TRAPPopathies”. One such disorder is NIBP syndrome, characterized by microcephaly and intellectual disability, and caused by mutations of NIBP/TRAPPC9, a crucial and unique member of TRAPPII. To investigate the neural cellular/molecular mec...

We have an operant model of reaching and grasping in which detrimental bone remodeling is observed rather than beneficial adaptation when rats perform a high‐repetition, high‐force (HRHF) task long term. Here, adult female Sprague–Dawley rats performed an intense HRHF task for 18 weeks, which we have shown induces radial trabecular bone osteopenia....

The objective of this study was to assess the prognostic potential of magnetic resonance (MR)-detected meniscal degeneration in relation to incident destabilizing meniscal tears (radial, complex, root, or macerated) or accelerated knee osteoarthritis (AKOA). We used existing MR data from a case-control study of 3 groups from the Osteoarthritis Init...

Dupuytren disease is a benign, progressive fibroproliferative disorder of the hands. To date, only one pharmacotherapy (clostridial collagenase) has been approved for use in Dupuytren disease. There is a great need for additional nonsurgical methods that can be used to either avoid the risks of invasive treatments or help minimize recurrence rates...

Context Adults with cerebral palsy (CP) display a higher prevalence of cardiometabolic disease compared with the general population. Studies examining cardiometabolic disease risk in children with CP are limited. Objective The purpose of this study was to determine if children with CP exhibit higher cardiometabolic risk than typically developing c...

Vagal fibers travel inside fascicles and form branches to innervate organs and regulate organ functions. Existing vagus nerve stimulation (VNS) therapies activate vagal fibers non-selectively, often resulting in reduced efficacy and side effects from non-targeted organs. The transverse and longitudinal arrangement of fibers inside the vagal trunk w...

Objective: Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome....

Aims: To investigate layer and species variations in detrusor muscle strip responses to myogenic, neurogenic, and nicotinic and muscarinic receptor stimulations. Methods: Strips from bladders of 9 dogs and 6 human organ transplant donors were dissected from inner and outer longitudinal muscle layers, at least 1 cm above urethral orifices. Strips...

The extra-cellular-matrix (ECM) composition of scar tissue after myocardial infarction (MI)has been largely investigated. Although fibronectin and collagen are favorable for newmyocyte formation, other components that may increase the scar stiffness and reducethe remodeling of the ischemic area, remain to be identified. Our preliminary studiesident...

The effectiveness of manual therapy in reducing the catabolic effects of performing repetitive intensive force tasks on bones has not been reported. We examined if manual therapy could reduce radial bone microstructural declines in adult female Sprague–Dawley rats performing a 12-week high-repetition and high-force task, with or without simultaneou...

This book presents an evidence-based mechanism explaining how and why musculoskeletal disorders (MSDs) develop. The mechanism of damage leading to MSDs is known as "fatigue failure", well known as the process by which materials fail when exposed to repeated stress. Understanding this process provides numerous insights into musculoskeletal tissue da...

This chapter examines the influences of various personal characteristics with respect to the development of musculoskeletal disorders (MSDs). It focuses on three primary personal characteristics, specifically those of age, sex, and anthropometry. The chapter discusses certain disease states that influence the expression of MSDs. Deterioration of mu...

The traditional domain of fatigue failure analysis has been in the analysis of the fatigue life of engineering materials such as metals, plastics, and composite materials. As complicated as the fatigue failure process can be in inert materials when one adds dynamic biological materials to the mix, an entirely new dimension of complexity is introduc...

This chapter focuses on the responses of various musculoskeletal tissues to the application of physical loads. It discusses some important fundamentals of materials science, the mechanical characteristics of musculoskeletal tissues, and the way they respond to different types of loading. The chapter then discusses the principles of fatigue failure....

Injuries in musculoskeletal and neural tissues can occur via a variety of mechanisms ranging from direct lacerations or mechanical deformation to indirect causes, and/or the accumulation of degenerative changes and therefore fatigue damage, due to repeated overuse, aging, or repeated sports injuries. Under normal conditions, an acute inflammatory r...

An important first step in assessing the risk of stressful tasks is to use the science of biomechanics to calculate the loads imposed on susceptible joints. This chapter discusses the fundamentals of biomechanics that are important to the understanding of how musculoskeletal tissues are stressed, and their reactions to this stress. Newton's first l...

This chapter describes techniques derived from fatigue failure theory that can be utilized to assess the risk associated with injury to musculoskeletal tissues under a variety of loading conditions. The relationship between applied stress and the number of cycles to failure in a material is exponential in nature and is typically described in an S–N...

This chapter presents evidence supporting the notion that fatigue failure may be an important etiological factor in the development of MSDs. Ex vivo testing of musculoskeletal tissues indicates that a classic fatigue failure in response to repeated stress is observed for every system component tested. Studies examining the fatigue loading responses...

Musculoskeletal disorders (MSDs) account for a large societal and economic burden throughout the world. In this chapter, the authors begin by providing a brief review of some of the more common MSDs, providing descriptions and characteristic features of the disorders, prevalence and incidence data, relevant anatomy and pathology, and the risk facto...

This chapter provides a systems overview of the nervous system, briefly defining central, peripheral, and automatic nervous systems. It describes interactions of peripheral and then central nervous systems (CNS) that interact with the musculoskeletal system. The chapter then describes pain, pain exacerbation, and pain persistence since pain symptom...

Fatigue failure theory provides several key insights that are helpful in assessing cumulative damage development in materials exposed to repeated stress. Some of these techniques can be readily implemented in easy‐to‐use musculoskeletal disorders risk assessment tools. This chapter describes the development, use, and validation of three fatigue fai...

This chapter details some of the insights and methods that may be useful in both assessing risk and preventing musculoskeletal disorder (MSD) development. In terms of MSD prevention, one goal is clearly to minimize the cumulative load experienced by a worker to an acceptable level of risk for both mono‐task and multi‐task jobs. An essential truth o...

This chapter discusses basic principles that appear to be useful in the treatment and rehabilitation of musculoskeletal injuries. It provides some specific advice for reducing the risk of developing musculoskeletal disorders in the occupational setting. The chapter describes procedures that may help reduce the pain and promote the healing process w...

This chapter discusses prior models for musculoskeletal disorder (MSD) risk assessment, and important implications regarding risk assessment should MSDs be the result of a fatigue failure process. The Revised National Institute for Occupational Safety and Health Lifting Equation is a widely used method of assessing the risk associated with manual l...

This chapter highlights some of the areas where research is needed to better understand fatigue failure processes in the human body, which will hopefully lead not only to better design of jobs but also to better overall musculoskeletal health through life. Statistical variability is an important issue with respect to fatigue testing and using an ap...

The musculoskeletal system is composed of a variety of specialized forms of tissues, including skeletal muscles, tendons, bones, joints, ligaments, and associated connective tissues. It also includes the nerves and blood vessels that bring innervation and blood supply to these structures. In this chapter, the authors discuss the basic structure and...

Afferent and efferent fibers in the vagus travel inside nerve fascicles and form branches to innervate organs and regulate organ functions. The organization of fibers and fascicles in the vagus trunk, with respect to the functions they mediate and the organs they innervate, remains largely unknown. Accordingly, it is unknown whether that anatomical...

This study aimed to identify potential lateralization of bladder function. Electrical stimulation of spinal roots or the pelvic nerve’s anterior vesical branch was performed bilaterally in female dogs. The percent difference between the left and right stimulation-induced increased detrusor pressure was determined. Bladders were considered left or r...

Manual therapies have been practiced for centuries, yet little research has been performed to understand their efficacy and almost no animal research has been performed to inform mechanisms of action. The methods of manual therapy practice are quite varied and present a challenge for scientists to model the treatments and perform research using rod...

Work-related musculoskeletal disorders associated with intense repetitive tasks are highly prevalent. Painful symptoms associated with such disorders can be attributed to neuropathy. In this study, we characterized the neuronal discharge from the median nerve in rats trained to perform an operant repetitive task. After 3-weeks of the task, rats dev...

Background: Repetitive strain injuries caused by repetitive occupational work are difficult to prevent for multiple reasons. Therefore, we examined the effectiveness of manual therapy (MT) with rest to treat the inflammation and fibrosis that develops through the performance of a repetitive task. We hypothesized that this treatment would reduce tas...

Background context: Individual characteristics can influence outcomes after injury. Our previous work in individuals with early-acute low back pain (LBP) identified subgroups (clusters) with specific biopsychosocial features that recovered poorly or well by 6 months. Purpose: This study extends on that work by revealing the short- and long-term...

While the effects of physical risk factors on MSD development have been a primary focus of musculoskeletal research, psychological stressors, and certain personal characteristics (e.g., aging, sex, and obesity) are also associated with increased MSD risk. The psychological and personal characteristics listed above share a common characteristic: all...

Musculoskeletal conditions are known to involve biological, psychological, social and, often, lifestyle elements. However, these domains are generally considered in isolation from each other. This siloed approach is unlikely to be adequate to understand the complexity of these conditions and likely explains a major component of the disappointing ef...

Background We examined the effectiveness of a manual therapy consisting of forearm skin rolling, muscle mobilization, and upper extremity traction as a preventive treatment for rats performing an intensive lever-pulling task. We hypothesized that this treatment would reduce task-induced neuromuscular and tendon inflammation, fibrosis, and sensorimo...

We determined the effect of pelvic organ decentralization and reinnervation one year later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7 and hypogastric nerves. After exclusions, 8 were reinnervated 12 months p...

This study determined the effect of pelvic organ decentralization and reinnervation one year later on the contribution of muscarinic and purinergic receptors to ex-vivo, nerve-evoked, bladder smooth muscle contractions. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of...

The pathogenesis of human immunodeficiency virus associated neurological disorders is still not well understood, yet is known to result in neurological declines despite combination anti-retroviral therapy. HIV-1 transgenic (Tg26) mice contain integrated non-infectious HIV-1 proviral DNA. We sought to assess the integrity of neurocognitive function...

Objective Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many individuals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to; (1) evaluate whether promising and potentiall...

Aim: To examine the chronic effect of force on mRNA and protein expression levels of fibrosis-related genes in flexor digitorum muscles in a rat model of repetitive overuse injury that induces muscle fibrosis at high force levels. Materials and methods: Two groups of rats were trained to perform a voluntary repetitive lever-pulling task at eithe...

Objective Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many individuals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to; (1) evaluate whether promising and potentiall...

Objective: Low back pain (LBP) is one of the most disabling and costly conditions worldwide. It remains unclear why many individuals experience persistent and recurrent symptoms after an acute episode whereas others do not. A longitudinal cohort study was established to address this problem. We aimed to; (1) evaluate whether promising and potential...

Purpose/Aim We recently found that blocking CCN2 signaling using a monoclonal antibody (FG-3019) may be a novel therapeutic strategy for reducing overuse-induced tissue fibrosis. Since CCN2 plays roles in osteoclastogenesis, and persistent performance of a high repetition high force (HRHF) lever pulling task results in a loss in trabecular bone vol...

Activation of κ opioid receptor (KOR) produces analgesia, antipruritic effect, sedation and dysphoria. To characterize neuroanatomy of KOR at high resolutions and circumvent issues of specificity of KOR antibodies, we generated a knock-in mouse line expressing KOR fused at the C terminus with the fluorescent protein tdTomato (KtdT). The selective K...

Background: Osteoarthritis is generally a slowly progressive disorder. However, at least 1 in 7 people with incident knee osteoarthritis develop an abrupt progression to advanced-stage radiographic disease, many within 12 months. We summarize what is known - primarily based on findings from the Osteoarthritis Initiative - about the risk factors an...

Background: We aimed to determine if composite structural measures of knee osteoarthritis (KOA) progression on magnetic resonance (MR) imaging can predict the radiographic onset of accelerated knee osteoarthritis. Methods: We used data from a nested case-control study among participants from the Osteoarthritis Initiative without radiographic KOA...

Introduction In our preceding paper, we concluded that Pelvic Girdle Pain (PGP) should be taken seriously. Still, we do not know its causes. Literature reviews on treatment fail to reveal a consistent pattern, and there are patients who do not respond well to treatment. We designated the lack of progress in research and in the clinic as ‘deadlock’,...

Encapsulation of median nerves is a hallmark of overuse‐induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG‐3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develop...