Joseph Lesnak

• The University of Texas at Dallas

The peripheral nervous system has been widely implicated in pathological conditions that exhibit distinct clinical presentations in men and women, most notably in chronic pain disorders. Here, we explored this sexual dimorphism at a molecular level. We expanded the available omics landscape in the PNS to include quantitative proteomics of the human...

Introduction Pregabalin, which acts on the α 2 δ-1 subunit of voltage-gated calcium channels, relieves ≥50% of pain in a third of individuals with fibromyalgia. Thus far, preclinical studies of pregabalin have predominantly used male animals. Objectives The purpose of our study was to investigate potential sex differences in the analgesic efficacy...

Intoduction: Common outcome measures for chronic neck pain are the Patient-Specific Functional Scale (PSFS) and the neck disability index (NDI). The primary aim was to categorize the top-rated, patient-selected functional activity limitations of the PSFS to determine if there were consistent limited functional activities for individuals with chroni...

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted f...

Diabetic neuropathy is frequently accompanied by pain and loss of sensation attributed to axonal dieback. We recovered dorsal root ganglia (DRGs) from 90 organ donors, 19 of whom had medical indices for diabetic painful neuropathy (DPN). Nageotte nodules, dead sensory neurons engulfed by non-neuronal cells, were abundant in DPN DRGs and accounted f...

It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression m...

Activity induced muscle pain increases release of interleukin 1 beta (IL1b) in muscle macrophages and the development of pain is prevented by blockade of IL1b. Brain derived neurotrophic factor (BDNF) is released from sensory neurons in response to IL1b and mediates both inflammatory and neuropathic pain. Thus, we hypothesized that metabolites rele...

Purpose of Review Individuals with post-acute sequelae of SARS-CoV-2 (PASC) complain of persistent musculoskeletal pain. Determining how COVID-19 infection produces persistent pain would be valuable for the development of therapeutics aimed at alleviating these symptoms. Recent Findings To generate hypotheses regarding neuroimmune interactions in...

We developed an animal model of activity-induced muscle pain that is dependent on local macrophage activation and release of interleukin-1β (IL-1β). Activation of purinergic type 2X (P2X) 7 receptors recruits the NOD-like receptor protein (NLRP) 3 and activates Caspase-1 to release IL-1β. We hypothesized that pharmacological blockade of P2X7, NLRP3...

Rigorous experimental design with transparent reporting in biomedical science reduces risk of bias and allows for scientists to judge the quality of the research. Basic factors of rigor such as blinding, randomization, power analysis, and inclusion of both sexes impact the reproducibility by reducing experimental bias. We designed a systematic stud...

Routine physical activity reduces the onset of pain and exercise is a first line treatment for individuals who develop chronic pain. In both preclinical and clinical research regular exercise (routine exercise sessions) produces pain relief through multiple mechanisms such as alterations in the central and peripheral nervous system. More recently,...

Induction of muscle pain triggers a local immune response to produce pain and this mechanism may be sex and activity level dependent. The purpose of this study was to measure the immune system response in the muscle following induction of pain in sedentary and physically active mice. Muscle pain was produced via an activity-induced pain model using...

Chronic pain is a significant health problem associated with disability and reduced quality of life. Current management of chronic pain is inadequate with only modest effects of pharmacological interventions. Thus, there is a need for the generation of analgesics for treating chronic pain. While preclinical and clinical studies demonstrate the anal...

Objective Preoperative exercise (prehabilitation) is commonly used as a method to reduce pain and improve function postoperatively. The purpose of this systematic review was to determine therapeutic benefits of preoperative exercise on postoperative pain, function, quality of life, and risk of complications across various types of surgeries. Metho...

Induction of muscle pain triggers a local immune response to produce pain and this mechanism may be sex and activity level dependent. The purpose of this study was to measure the immune system response in the muscle following induction of pain in sedentary and physically active mice. Muscle pain was produced via an activity-induced pain model using...

Currently, there is a need for the generation of non-opioid analgesics for treating chronic pain. Preclinical and clinical studies demonstrate the analgesic effects of testosterone. However, treatment with testosterone is not feasible due to adverse effects. Selective androgen receptor modulators (SARMs) were developed to overcome these limitations...

A growing number of individuals report prolonged symptoms following acute Coronavirus-19 (COVID-19) infection, known as post-COVID-19 condition (post-COVID-19). While studies have emerged investigating the symptom sequelae of post-COVID-19, there has been limited investigation into the characterization of pain, fatigue, and function in these indivi...

We developed an animal model of activity-induced muscle pain that is dependent on local macrophage activation and release of interleukin-1β (IL-1β). Activation of purinergic type 2X (P2X) 7 receptors recruits the NOD-like receptor protein 3 (NLRP3) and activates caspase-1 release IL-1β. We hypothesized that pharmacological blockade of P2 × 7 recept...

The purpose of this study was to develop a clinically relevant mouse model of CFS to allow for the testing of underlying mechanisms and development of novel treatment interventions. Mice were injected with either lipopolysaccharide (LPS) or Poly I:C systemically (0.1- 1.0 mg/kg LPS, i.p. or 0.6-6mg/kg Poly I:C) and compared to a vehicle control inj...

There is a need for the generation of non-opioid analgesics for chronic pain. The analgesic effects of testosterone have been demonstrated in preclinical and clinical studies. However, treatment with testosterone is not clinically feasible due to adverse effects. Select androgen receptor modulators (SARMs) were developed to overcome adverse effects...

This research sought to identify the relation of pain, fatigue, disease impact, and psychological factors with physical function in individuals with post-COVID-19 syndrome (post-COVID), fibromyalgia, chronic fatigue syndrome (CFS), and those with combined diagnoses of post-COVID, FMS, and/or CFS (multi-Dx). Individuals with post-COVID, fibromyalgia...

We developed an activity-induced musculoskeletal pain model that produces behavioral sex differences in which females develop widespread hyperalgesia of longer duration, while males develop localized pain for shorter durations. Previously, we determined that testosterone mediates the behavioral phenotype in male and female mice, and that there are...

Exercise produces analgesia through multiple peripheral, spinal, and supraspinal pathways. However, uncovering these pathways one by one is time consuming, biased based on prior literature, and requires significant number animals to be tested. RNA sequencing allows for discovery of numerous transcriptional differences and can lead to the discovery...

Resistance training-based exercise is commonly prescribed in the clinic for the treatment of chronic pain. Mechanisms of aerobic exercise for analgesia are frequently studied, while little is known regarding resistance training mechanisms. We developed a resistance training model in mice and hypothesized resistance training would protect against de...

Exercise is an effective and recommended treatment for chronic pain conditions. In the rehabilitation setting, both aerobic and resistance training (RT) exercise programs are recommended for various chronic pain conditions. However, animal research has focused on the utilization of aerobic based exercise programs. Therefore, the purpose of this pro...

Physical activity has become a first-line treatment in rehabilitation settings for individuals with chronic pain. However, research has only recently begun to elucidate the mechanisms of exercise-induced analgesia. Through the study of animal models, exercise has been shown to induce changes in the brain, spinal cord, immune system, and at the site...

Chronic widespread pain conditions are more prevalent in women than men suggesting a role for gonadal hormones in the observed differences. Previously, we showed female mice, compared to male, develop widespread, more severe, and longer duration hyperalgesia in a model of activity-induced muscle pain. We hypothesized testosterone protects males fro...

Conditions with chronic widespread non-inflammatory muscle pain, such as fibromyalgia, have complex etiologies with numerous proposed mechanisms for their pathophysiology of underlying chronic pain. Advancements in neuroimaging have allowed for the study of brain function and connectivity in humans with these conditions, while development of animal...

Context: Resistance training exercise prescription is often based on exercises performed at a percentage of a 1 repetition maximum (1 RM). Following knee injury, there is no consensus when a patient can safely perform 1 RM testing. Resistance training programs require the use of higher loads and loads used in knee injury rehabilitation may be too...

Currently, there are no established biomarkers for the diagnosis or symptoms of pain and fatigue in individuals with fibromyalgia (FM). The objective of this study was to identify potential biomarkers in individuals with FM, and to correlate these putative biomarkers with FM-symptoms using a targeted metabolomics approach. The current study was a s...

Background: A hand-held dynamometer (HHD) offers a reliable and valid method to quantify quadriceps strength in a clinical environment. While measures of peak strength provide functional insights, most daily activities are performed quickly and do not require maximum strength. Rate of torque development (RTD) measures better reflect both the deman...