ENA-001 Reverses Xylazine/Fentanyl Combination-Induced Respiratory Depression in Rats: A Qualitative Pilot Study.

Xylazine exacerbates the respiratory depression induced by fentanyl. Because xylazine is a non-opioid, it is resistant to reversal by opioid receptor antagonists such as naloxone (e.g.

Managing the neuroinflammatory pain of endometriosis in light of chronic pelvic pain.

Introduction: Endometriosis affects 5% to 10% of reproductive age women and may be associated with severely painful and debilitating symptoms as well as infertility. Endometriosis involves hormonal fluctuations, angiogenesis, neurogenesis, vascular changes and neuroinflammatory processes. The neuroinflammatory component of endometriosis makes it a systemic disorder, similar to other chronic epithelial inflammatory conditions.

A Novel Formulation of Ketorolac Tromethamine (NTM-001) in Continuous Infusion in Adults with and without Renal Impairment: A Randomized Controlled Pharmacologic Study.

Introduction: There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment.

Methods: Participants (≥ 65 years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89 mL/min for mild and 30-59 mL/min for moderate. Subjects were randomized to receive a loading dose of 6.

Opioid Use and Gut Dysbiosis in Cancer Pain Patients.

Opioids are commonly used for the management of severe chronic cancer pain. Their well-known pharmacological effects on the gastrointestinal system, particularly opioid-induced constipation (OIC), are the most common limiting factors in the optimization of analgesia, and have led to the wide use of laxatives and/or peripherally acting mu-opioid receptor antagonists (PAMORAs). A growing interest has been recently recorded in the possible effects of opioid treatment on the gut microbiota.

Innovative Applications of Telemedicine and Other Digital Health Solutions in Pain Management: A Literature Review.

Since the COVID-19 pandemic, healthcare systems are facing extraordinary challenges. Our approaches to medicine have changed and created a whole new generation of people who have chronic pain. Various medical services were postponed.

Bispecific Sigma1R-Antagonist/MOR-Agonist Compounds for Pain.

Recent research has significantly advanced an understanding of sigma receptors, which consist of two distinct subtypes designated as S1R and S2R ( and gene products, respectively). Both subtypes have recently been cloned and their crystal structures have been published. As a result, highly selective S1R and S2R agonist and antagonist ligands are now available.

Recent Developments in Sigma-2 Receptor Compounds for Pain.

After years of enigmatic pharmacology, non-selective ligands, and uncertain clinical application, sigma receptors have emerged as interesting therapeutic drug discovery-development targets. Two subtypes of sigma receptors have now been cloned, sigma-1 receptor (S1R) and sigma-2 receptor (S2R), and there has been much complementary and converging information from advances in molecular biology, computer modeling, virtual screening, and in vitro and in vivo testing. One of several evolving areas of therapeutic potential is for the treatment of pain.

Bracketing Estimation of Intentional Polysubstance Use in the United States.

Evidence from diverse sources suggests that persons who have a substance use disorder (SUD) often have problems with one or more additional substances, a situation broadly, if imprecisely, termed polysubstance use or more preferably multiple substance use disorder (mSUD). Because of the heavy toll of maladaptive neuronal dysregulation, morbidity, and mortality of SUDs, and increasingly of mSUD, on the individual, their families, the healthcare system, insurers, regulators, and society at large, it seems of value to have an estimate of the prevalence of mSUD. This turns out to be surprisingly difficult, due to nebulous or disparate definitions and to weaknesses in data acquisition methodology.

Incorporation of "Artificial Intelligence" for Objective Pain Assessment: A Comprehensive Review.

Pain is a significant health issue, and pain assessment is essential for proper diagnosis, follow-up, and effective management of pain. The conventional methods of pain assessment often suffer from subjectivity and variability. The main issue is to understand better how people experience pain.

A New Rat Study Suggests There May Be a Biologic Explanation for Higher Fentanyl Mortality in Men Than in Women.

Could it be possible that we should give some weight to the contribution of biological differences as contributors to the greater fentanyl mortality in males than in females? Most current explanations for a sex difference are based largely on psychosocial and other non-physiologic contributions. Our recent findings suggest a biological contribution. This could have broad implications for the interpretation and prevention of fentanyl overdose deaths.

Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial.

Background: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion.

The Challenges of Pain Assessment in Geriatric Patients With Dementia: A Review.

Pain in dementia patients is common, poorly measured, and undertreated. It is important to discuss the challenges in the pain assessment and management to find a possible solution for adequate pain management. The aim of this article is to discuss the challenges in the assessment of pain in geriatric patients with dementia.

A Randomized Controlled Trial of a Novel Formulation of Ketorolac Tromethamine for Continuous Infusion (NTM-001) in Healthy Volunteers.

Introduction: There is an urgent unmet medical need for a safe, effective, nonopioid analgesic agent for postoperative pain control.

Methods: This first-in-man study was designed to explore a data-informed, model-based candidate dosage regimen and safety of a novel formulation of ketorolac tromethamine (NTM-001) delivered as a 12.5-mg intravenous (IV) bolus followed immediately by 3.

Identifying risk factors for chronic postsurgical pain and preventive measures: a comprehensive update.

Introduction: Chronic postsurgical pain (CPSP) is a prevalent condition that can diminish health-related quality of life, cause functional deficits, and lead to patient distress. Rates of CPSP are higher for certain types of surgeries than others (thoracic, breast, or lower extremity amputations) but can occur after even uncomplicated minimally invasive procedures. CPSP has multiple mechanisms, but always starts as acute postsurgical pain, which involves inflammatory processes and may encompass direct or indirect neural injury.

The Sex Data Gap Within Implantable Cardioverter Defibrillator (ICD) Studies: A Retrospective Study of Literature From 1980 Until 2022.

Implantable cardioverter defibrillators (ICDs) are a form of cardiac therapy used to prevent death in patients at risk for sudden heart failure. Using 100 articles from the introduction of ICDs until now, a retrospective literature review was conducted. These studies were analyzed for sex disparity over the past 40 years.

What Do We Need to Know About Rising Rates of Idiopathic Pulmonary Fibrosis? A Narrative Review and Update.

The most common type of idiopathic interstitial pneumonia is idiopathic pulmonary fibrosis (IPF), an irreversible, progressive disorder that has lately come into question for possible associations with COVID-19. With few geographical exceptions, IPF is a rare disease but its prevalence has been increasing markedly since before the pandemic. Environmental exposures are frequently implicated in IPF although genetic factors play a role as well.

Pharmacotherapeutic management of trigeminal neuropathic pain: an update.

Introduction: Guidelines recommend a number of pharmacotherapeutic options used as monotherapy or in combination with others for treating the pain of trigeminal neuropathy.

Areas Covered: The authors examine the pharmacotherapeutic options for treating trigeminal neuralgia and supporting evidence in the literature. Guidelines reported the most effective treatment for trigeminal neuropathy, in particular trigeminal neuralgia, appears to be carbamazepine or oxcabazepine, but side effects can be treatment limiting.

Effects of Digoxin in Heart Failure (HF) With Reduced Ejection Fraction (EF).

In this review, we evaluated the literature on the benefits and deleterious effects of digoxin in heart failure (HF) with reduced ejection fraction (EF). Although digoxin was considered an effective treatment for HF, the supporting evidence is conflicting. Before the conventional use of modern HF therapies, digoxin was widely used for symptomatic relief on these patients.

Opioid Therapy in Cancer Patients and Survivors at Risk of Addiction, Misuse or Complex Dependency.

A clinical conundrum can occur when a patient with active opioid use disorder (OUD) or at elevated risk for the condition presents with cancer and related painful symptoms. Despite earlier beliefs that cancer patients were relatively unaffected by opioid misuse, it appears that cancer patients have similar risks as the general population for OUD but are more likely to need and take opioids. Treating such patients requires an individualized approach, informed consent, and a shared decision-making model.

The epidemiology of apnoea of prematurity.

What Is Known And Objective: Many premature infants less than 37 weeks gestational age (GA), and almost all infants less than 28 weeks GA, will experience apnoea of prematurity (AOP)-a cessation of respiration for 20 or more seconds (or less than 20 s if accompanied by other signs). Because the treatment options for AOP are so limited, we explore its epidemiology, with the ultimate hope of learning how to decrease its incidence.

Comment: Although AOP usually resolves with maturation of the respiratory system, many short- and long-term negative effects are correlated statistically with AOP (although direct causality has not been established).

The limited management options for apnoea of prematurity.

What Is Known And Objective: About 10% of all infants are born prematurely. Almost all of those of gestational age less than about 30 weeks, and about half of those of gestational age up to about 35 weeks, are subject to unpredictable interruptions of breathing-known as "apnoea of prematurity" (AOP). We present a synopsis of the problem and point out the limited management options.