Epigenomic landscape of the human dorsal root ganglion: sex differences and transcriptional regulation of nociceptive genes.

Gene expression is influenced by chromatin architecture via controlled access of regulatory factors to DNA. To better understand gene regulation in the human dorsal root ganglion (hDRG) we used bulk and spatial transposase-accessible chromatin technology followed by sequencing (ATAC-seq). Using bulk ATAC-seq, we detected that in females diverse differentially accessible chromatin regions (DARs) mapped to the X chromosome and in males to autosomal genes.

Peripheral Neuroinflammation and Pain: How Acute Pain Becomes Chronic.

The number of individuals suffering from severe chronic pain and its social and financial impact is staggering. Without significant advances in our understanding of how acute pain becomes chronic, effective treatments will remain out of reach. This mini review will briefly summarize how critical signaling pathways initiated during the early phases of peripheral nervous system inflammation/ neuroinflammation establish long-term modifications of sensory neuronal function.

Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A.

The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors.

Development of the Illinois Surgical Quality Improvement Collaborative (ISQIC): Implementing 21 Components to Catalyze Statewide Improvement in Surgical Care.

Introduction: In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.

Methods: ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem.

N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes.

Background: The transient receptor potential vanilloid 1 (TRPV1) participates in thermosensation and inflammatory pain, but its immunomodulatory mechanisms remain enigmatic. N-Oleoyl dopamine (OLDA), an endovanilloid and endocannabinoid, is a TRPV1 agonist that is produced in the central nervous system and the peripheral nervous system. We studied the anti-inflammatory effects and TRPV1-dependent mechanisms of OLDA in models of inflammation and sepsis.

Occurrence and perceived effectiveness of activities used to decrease chemotherapy-induced peripheral neuropathy symptoms in the feet.

Purpose: Investigate the reported use and perceived effectiveness of self-care activities for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in the feet.

Methods: Cancer survivors with CIPN (n = 405) completed a questionnaire that assessed the use and perceived effectiveness of 25 self-care activities. Effectiveness was rated on a 0 (not at all) to 10 (completely effective) numeric rating scale.

Implementation and Effects of a Team-Based Quality Improvement Training Program Across a Health System: The Northwestern Medicine Academy for Quality and Safety Improvement.

Background: Professional organizations emphasize the need to train health care professionals in quality improvement (QI). Many reports of QI education programs involve small numbers of participants. Little is known about QI education programs on a larger scale and whether participants subsequently engage in QI activities.

Differential methylation and expression of genes in the hypoxia-inducible factor 1 signaling pathway are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors and with preclinical models of chemotherapy-induced neuropathic pain.

Background: Paclitaxel is an important chemotherapeutic agent for the treatment of breast cancer. Paclitaxel-induced peripheral neuropathy (PIPN) is a major dose-limiting toxicity that can persist into survivorship. While not all survivors develop PIPN, for those who do, it has a substantial negative impact on their functional status and quality of life.

Long-Term Trends in Postoperative Opioid Prescribing, 1994 to 2014.

Unlabelled: Opioids are routinely prescribed to manage acute postoperative pain, but changes in postoperative opioid prescribing associated with the marketing of long-acting opioids such as OxyContin have not been described in the surgical cohort.

Methods: Using a large commercial claims data set, we studied postoperative opioid prescribing after selected common surgical procedures between 1994 and 2014. For each procedure and year, we calculated the mean postoperative morphine milligram equivalents (MME) filled on the index prescription and assessed the proportion of patients who filled a high-dose prescription (≥350 MME).

AAAPT Diagnostic Criteria for Acute Pain Following Breast Surgery.

Acute pain after breast surgery decreases the quality of life of cancer survivors. Previous studies using a variety of definitions and methods report prevalence rates between 10% and 80%, which suggests the need for a comprehensive framework that can be used to guide assessment of acute pain and pain-related outcomes after breast surgery. A multidisciplinary task force with clinical and research expertise performed a focused review and synthesis and applied the 5 dimensional framework of the AAAPT (Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks [ACTTION], American Academy of Pain Medicine [AAPM], American Pain Society [APS] Pain Taxonomy) to acute pain after breast surgery.

Signaling pathways and gene co-expression modules associated with cytoskeleton and axon morphology in breast cancer survivors with chronic paclitaxel-induced peripheral neuropathy.

Background: The major dose-limiting toxicity of paclitaxel, one of the most commonly used drugs to treat breast cancer, is peripheral neuropathy (paclitaxel-induced peripheral neuropathy). Paclitaxel-induced peripheral neuropathy, which persists into survivorship, has a negative impact on patient’s mood, functional status, and quality of life. Currently, no interventions are available to treat paclitaxel-induced peripheral neuropathy.

Perturbations in neuroinflammatory pathways are associated with paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Paclitaxel is a common chemotherapy drug associated with the development of chronic paclitaxel-induced peripheral neuropathy (PIPN). PIPN is associated with neuroinflammatory mechanisms in pre-clinical studies. Here, we evaluated for differential gene expression (DGE) in peripheral blood between breast cancer survivors with and without PIPN and for neuroinflammatory (NI) related signaling pathways and whole-transcriptome profiles from other experiments.

Hospital-Level Cardiovascular Management Practices in Kerala, India.

Background Hospital management practices are associated with cardiovascular process of care measures and patient outcomes. However, management practices related to acute cardiac care in India has not been studied. Methods and Results We measured management practices through semistructured, in-person interviews with hospital administrators, physician managers, and nurse managers in Kerala, India between October and November 2017 using the adapted World Management Survey.

Deleterious Effects of Higher Body Mass Index on Subjective and Objective Measures of Chemotherapy-Induced Peripheral Neuropathy in Cancer Survivors.

Context: Recent, albeit, limited evidence suggests that body mass index (BMI) may be a modifiable risk factor to reduce the deleterious effects of chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors.

Objectives: To evaluate for differences in demographic, clinical, pain, sensation, and balance characteristics among three BMI groups. We hypothesized that as BMI increased, survivors would report higher pain intensity scores and have significant decrements in measures of sensation and balance.

Transcription factor Sp4 is required for hyperalgesic state persistence.

Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months.

Age-related differences in patient-reported and objective measures of chemotherapy-induced peripheral neuropathy among cancer survivors.

Purpose: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors.

Methods: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory, and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (< 65 n = 260 versus ≥ 65 n = 165) using parametric and nonparametric tests.

Pain Management and Opioid Regulation: Continuing Public Health Challenges.

The still-growing US opioid epidemic lies at the intersection of two major public health challenges: reducing suffering from pain and containing the rising toll of harms associated with the use of opioids medications. Responding successfully to these challenges requires a substantial investment in surveillance and research on many fronts and a coordinated policy response by federal and state agencies and stakeholder organizations.A 2017 report of the National Academies of Sciences, Engineering and Medicine (NASEM) called for improved methods of measuring pain and the effects of alternative modalities of treatment as well as intensive surveillance of opioid-related harms; urged a long-term cultural transformation of how pain is perceived, assessed and treated; and outlined a comprehensive and balanced public health framework to guide Food and Drug Administration approval, monitoring, and review of opioids.

Expression of mitochondrial dysfunction-related genes and pathways in paclitaxel-induced peripheral neuropathy in breast cancer survivors.

Background: Paclitaxel is one of the most commonly used drugs to treat breast cancer. Its major dose-limiting toxicity is paclitaxel-induced peripheral neuropathy (PIPN). PIPN persists into survivorship and has a negative impact on patient's mood, functional status, and quality of life.

Contribution of Loss of Large Fiber Function to Pain in 2 Samples of Oncology Patients.

Objectives: Numbness associated with neuropathic pain suggests the loss of function in myelinated, large diameter sensory neurons. The purpose of this study was to examine the relationships between pain severity and subjective (ie, severity of numbness) and objective (ie, loss of light touch sensations, vibration thresholds) measures of loss of large fiber function in adult survivors with chemotherapy-induced peripheral neuropathy (CIPN, n=426) and breast cancer patients with persistent postsurgical pain (n=80).

Material And Methods: For both samples, average pain and numbness were evaluated using a 0 to 10 numeric rating scale.

Phenotypic Characterization of Paclitaxel-Induced Peripheral Neuropathy in Cancer Survivors.

Context: Although paclitaxel is one of the most commonly used drugs to treat breast, ovarian, and lung cancers, little is known about the impact of paclitaxel-induced peripheral neuropathy (PIPN) on cancer survivors.

Objectives: The purposes of this study were to evaluate for differences in demographic and clinical characteristics as well as measures of sensation, balance, upper extremity function, perceived stress, symptom burden, and quality of life (QOL) between survivors who received paclitaxel and did (n = 153) and did not (n = 58) develop PIPN.

Methods: Pain characteristics associated with PIPN are described in detail.

Integrating Patient-Controlled Analgesia Using Implanted Intrathecal Pumps for Postoperative Pain Management: A Case Report.

Intrathecal patient-controlled analgesia (IT-PCA) through implanted intrathecal infusion pumps has been increasingly utilized for severe cancer and chronic noncancer pain management. However, its application for acute postoperative pain management has not been reported to date. We present a case of a patient with an implanted intrathecal pump for chronic nonmalignant back pain who underwent an extensive spinal fusion surgery.

Immediate and long-term effects of a team-based quality improvement training programme.

Background: Although many studies of quality improvement (QI) education programmes report improvement in learners' knowledge and confidence, the impact on learners' future engagement in QI activities is largely unknown and few studies report project measures beyond completion of the programme.

Method: We developed the Academy for Quality and Safety Improvement (AQSI) to prepare individuals, across multiple departments and professions, to lead QI. The 7-month programme consisted of class work and team-based project work.

Associations Between Perceived Stress and Chemotherapy-Induced Peripheral Neuropathy and Otoxicity in Adult Cancer Survivors.

Context: The most common adverse effects from neurotoxic chemotherapy are chemotherapy-induced neuropathy (CIPN), hearing loss, and tinnitus. Although associations between perceived stress and persistent pain, hearing loss, and tinnitus are documented, no studies have examined these associations in cancer survivors who received neurotoxic chemotherapy.

Objectives: In this cross-sectional study, we evaluated for associations between perceived stress and the occurrence of CIPN, hearing loss, and tinnitus, in 623 adult cancer survivors who received platinum and/or taxane compounds.