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BioRxiv : the Preprint Server For... Jun 2024Alcohol consumption produces acute analgesic effects, and people experiencing pain conditions may drink alcohol to alleviate discomfort. However, tolerance to the...
Alcohol consumption produces acute analgesic effects, and people experiencing pain conditions may drink alcohol to alleviate discomfort. However, tolerance to the analgesic properties of alcohol could prompt escalating consumption and dependence. Both nociception and alcohol-induced analgesia are under significant genetic control. Understanding the genetic architecture of these processes could inform better treatment options for people with pain conditions. This study aims to identify quantitative trait loci (QTL) driving variation in ethanol-induced analgesia across BXD recombinant inbred mouse lines. Male and female mice from 62 BXD strains received ethanol or saline oral gavage for five days and were tested for hot plate (HP) latency at baseline, Day 1, and Day 5. QTL mapping of HP phenotypes identified a significant provisional QTL on chromosome 17 for Day 1 HP latency in mice receiving ethanol. An additional highly suggestive QTL was present on chromosome 9 for the difference in pre- and post-ethanol thermal nociception. Candidate genes within QTL support intervals were provisionally identified using HP phenotypic correlations to transcriptomic database, expression QTL analysis, and other bioinformatics inquiries. The combined behavioral and bioinformatic analyses yielded strong ethanol analgesia candidate genes, specifically . Thus, the results of this genetic study of ethanol-induced analgesia in BXD mouse strains may contribute significantly to our understanding of the molecular basis for individual variation in the analgesic response to acute ethanol.
PubMed: 38948869
DOI: 10.1101/2024.06.17.599372 -
BioRxiv : the Preprint Server For... Jun 2024Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like...
Pain is a prominent and debilitating symptom in myotonic disorders, yet its physiological mechanisms remain poorly understood. This study assessed preclinical pain-like behavior in murine models of pharmacologically induced myotonia and myotonic dystrophy type 1 (DM1). In both myotonia congenita and DM1, impairment of the gene, which encodes skeletal muscle voltage-gated CLC-1 chloride channels, reduces chloride ion conductance in skeletal muscle cells, leading to prolonged muscle excitability and delayed relaxation after contraction. We used the CLC-1 antagonist anthracene-9- carboxylic acid (9-AC) at intraperitoneal doses of 30 or 60 mg/kg and HSA LR20b DM1 mice to model CLC-1-induced myotonia. Our experimental approach included pain behavioral testing, calcium imaging, and whole-cell current-clamp electrophysiology in mouse dorsal root ganglion (DRG) neurons. A single injection of 9-AC induced myotonia in mice, which persisted for several hours and resulted in long-lasting allodynic pain-like behavior. Similarly, HSA LR20b mice exhibited both allodynia and hyperalgesia. Despite these pain-like behaviors, DRG neurons did not show signs of hyperexcitability in either myotonic model. These findings suggest that myotonia induces nociplastic pain-like behavior in preclinical rodents, likely through central sensitization mechanisms rather than peripheral sensitization. This study provides insights into the pathophysiology of pain in myotonic disorders and highlights the potential of using myotonic mouse models to explore pain mechanisms and assess novel analgesics. Future research should focus on the central mechanisms involved in myotonia-induced pain and develop targeted therapies to alleviate this significant clinical burden.
PubMed: 38948724
DOI: 10.1101/2024.06.19.599732 -
Journal of Family Medicine and Primary... May 2024Healthcare work is a major risk for having musculoskeletal disorders (MSDs), including low back pain (LBP). This study aimed to estimate the prevalence of LBP and define...
BACKGROUND
Healthcare work is a major risk for having musculoskeletal disorders (MSDs), including low back pain (LBP). This study aimed to estimate the prevalence of LBP and define its associated risk factors among resident physicians.
MATERIAL AND METHODS
A descriptive cross-sectional survey was conducted among all resident physicians of all specialties in Abha city during the period from July 2020 to September 2020. Data were collected using an online pre-structured data collection tool. The Nordic Musculoskeletal Questionnaire (NMQ) (back pain section) was applied to assess the effect of LBP on the residents' ability to perform job duties effectively.
RESULTS
A total of 312 resident physicians responded. Their age ranged between 25 and 41 years. Males represented 57.7% of them. The prevalence of LBP was 64.7%. The most common reported aggravating factors for LBP were working in uncomfortable posture (73.3%), standing for long periods (64.4%), and long sitting sessions (51.5%). Regarding the pain-relieving factors, sleeping ranked first (60.4%), followed by taking analgesics (48.5%) and maintaining a good posture (35.6%). Multivariate logistic regression analysis revealed that obese subjects were at higher risk than underweight subjects to develop LBP (adjusted odds ratio (AOR) =6.18, 95% confidence interval (CI): 1.26-30.34, = 0.025). Compared to resident physicians without family history of back pain, those with such history were at almost 4-fold higher risk of developing LBP (AOR = 3.90, 95% CI: 2.33-6.52, < 0.001).
CONCLUSION
LBP is a very prevalent problem among resident physicians, particularly obese subjects and those with family history of back pain. LBP adversely impacts the work performance of the affected physicians.
PubMed: 38948619
DOI: 10.4103/jfmpc.jfmpc_1726_23 -
Frontiers in Pharmacology 2024"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and...
BACKGROUND
"Kratom" refers to an array of bioactive products derived from , a tree indigenous to Southeast Asia. Most kratom consumers report analgesic and stimulatory effects, and common reasons for use are to address mental and physical health needs, manage pain, and to reduce use of other substances. Natural-history studies and survey studies suggest that many kratom consumers perceive benefits from those uses, but such studies are unlikely to capture the full range of kratom-use experiences.
METHODS
We collected text data from Reddit posts from 2020-2022 to qualitatively examine conceptualizations, motivations, effects, and consequences associated with kratom use among people posting to social media. Reddit posts mentioning kratom were studied using template thematic analysis, which included collecting descriptions of kratom product types and use practices. Network analyses of coded themes was performed to examine independent relationships among themes, and between themes and product types.
RESULTS
Codes were applied to 329 of the 370 posts that comprised the final sample; 134 posts contained kratom product descriptions. As Reddit accounts were functionally anonymous, demographic estimates were untenable. Themes included kratom physical dependence (tolerance, withdrawal, or use to avoid withdrawal), perceived addiction (net detrimental effects on functioning), and quitting. Extract products were positively associated with reports of perceived addiction, dependence, and experiences of quitting kratom. Many used kratom for energy and self-treatment of pain, fatigue, and problems associated with opioid and alcohol; they perceived these uses as effective. Consumers expressed frustrations about product inconsistencies and lack of product information.
CONCLUSION
As in previous studies, kratom was deemed helpful for some and a hindrance to others, but we also found evidence of notable negative experiences with kratom products that have not been well documented in surveys. Daily kratom use may produce mild-moderate physical dependence, with greater severity being possibly more common with concentrated extracts; however, there are currently no human laboratory studies of concentrated kratom extracts. Such studies, and detailed kratom product information, are needed to help inform consumer decision-making.
PubMed: 38948457
DOI: 10.3389/fphar.2024.1412397 -
Integrated Pharmacy Research & Practice 2024Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is...
PURPOSE
Warfarin plays an important role in anticoagulation therapy despite the availability of the newest oral anticoagulants, and achieving optimal anticoagulation is challenging due to its narrow therapeutic range and variable dose. This study aimed to highlight polypharmacy and drug interactions in patients receiving warfarin therapy at Medani Heart Centre, Sudan.
METHODS
This retrospective hospital-based study was conducted from May 2017 to October 2018. Each concurrent medication prescribed for 104 patients was collected and checked for drug-drug interactions using Medscape Reference-Drug Interaction Checker. The data were analysed by using SPSS 20, and descriptive statistics were used.
RESULTS
The results revealed that 95.2% of patients had more than three medications in their profile, (3-5), (6-9) and more than 10 medications were prescribed for 40.4%, 44.2% and 10.6% of patients, respectively. A total of 93.3% of patients had drug-drug interactions, as follows: (1-5), (6-10), (11-15), (16-20) and more than 20 drug-drug interactions were found in 31.7%, 32.7%, 19.2%, 5.8% and 3.8% of patients, respectively. A total of 178 warfarin-drug interactions were identified in 88.5% of the patients. The INR ranged between 2 and 2.99 in 13.4% of patients, and INR values below 2 and above 5 were found in 44.2% and 21.2% of patients, respectively. Analgesics (n=54; 30.3%), cardiovascular drugs (n=51; 28.6%), and anticoagulants (n=46; 25.8%) were the most common drug classes that interact with warfarin. Significant and serious types of interactions with warfarin were found in 51% and 37.5% of patients, respectively.
CONCLUSION
This study highlights the complexity of managing warfarin therapy amid prevalent polypharmacy. A substantial majority of patients experienced multiple drug interactions. The identification of significant and serious interactions emphasizes the need for vigilant management strategies, including improved communication among healthcare professionals and targeted education for both providers and patients, to enhance the safety and efficacy of warfarin therapy.
PubMed: 38948431
DOI: 10.2147/IPRP.S458827 -
Cureus May 2024A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient...
A rare complication, 5-oxoproline-induced high anion gap metabolic acidosis (HAGMA) is associated with chronic acetaminophen use, predominantly reported in outpatient settings. However, its occurrence in hospitalized patients, particularly those with end-stage renal disease (ESRD), remains underreported. We present a case of a 74-year-old female with ESRD on hemodialysis who developed HAGMA highly suspicious for 5-oxoproline toxicity from acetaminophen usage following cardiac surgery. Despite a standard analgesic dose, the patient's renal impairment likely predisposed her to 5-oxoproline accumulation, resulting in severe metabolic acidosis. Discontinuation of acetaminophen led to the resolution of HAGMA, highlighting the importance of recognizing this rare but potentially life-threatening complication in the inpatient and critical care setting. This case suggests a potential interaction between acetaminophen metabolism and renal dysfunction in the pathogenesis of 5-oxoproline-induced HAGMA.
PubMed: 38947688
DOI: 10.7759/cureus.61328 -
Cureus May 2024In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was...
Lateness of Acetaminophen and Non-steroidal Anti-inflammatory Drug Administrations in a Retrospective Cohort of Medication Administration Records Among Patients After Cesarean Delivery.
INTRODUCTION
In an earlier study of patients after cesarean delivery, the concurrent versus alternating administration of acetaminophen and non-steroidal anti-inflammatory drugs was associated with a substantial reduction in total postoperative opioid use. This likely pharmacodynamic effect may differ if the times when nurses administer acetaminophen and non-steroidal anti-inflammatory drugs often differ substantively from when they are due. We examined the "lateness" of analgesic dose administration times, the positive difference if administered late, and the negative value if early.
METHODS
The retrospective cohort study used all 67,900 medication administration records for scheduled (i.e., not "as needed") acetaminophen, ibuprofen, and ketorolac among all 3,163 cesarean delivery cases at the University of Iowa between January 2021 and December 2023. Barcode scanning at the patient's bedside was used right before each medication administration.
RESULTS
There were 95% of doses administered over a 4.8-hour window, from 108 minutes early (97.5% one-sided upper confidence limit 105 minutes early) to 181 minutes late (97.5% one-sided lower limit 179 minutes late). Fewer than half of doses (46%, P <0.0001) were administered ±30 minutes of the due time. The intraclass correlation coefficient was approximately 0.11, showing that there were small systematic differences among patients. There likewise were small to no systematic differences in lateness based on concurrent administrations of acetaminophen and ibuprofen or ketorolac, time of the day that medications were due, weekday, year, or number of medications to be administered among all such patients within 15 minutes.
DISCUSSION
Other hospitals should check the lateness of medication administration when that would change their ability to perform or apply the results of analgesic clinical trials (e.g., simultaneous versus alternating administration).
PubMed: 38947679
DOI: 10.7759/cureus.61433 -
Journal of Surgery and Research 2024Damage to the peripheral and central nervous systems is frequently irreversible. Surgically induced neurological damage and anesthesia may result in catastrophic...
Damage to the peripheral and central nervous systems is frequently irreversible. Surgically induced neurological damage and anesthesia may result in catastrophic situations for patients and their families. The incidence of significant neurological complications during the perioperative period is examined in this article. In contrast to other organs like the kidney, heart, liver, lungs, and skeletal system, native neurological function cannot be replaced with artificial parts or devices soon. Ignoring brain function during the perioperative period has been a systemic problem in anesthesiology, even though the central and peripheral nervous systems are crucial. This bold claim is intended to draw attention to the fact that, unlike the circulatory and respiratory systems, which have been routinely monitored for decades, the brain and other neural structures do not have a standard monitoring during surgery and anesthesia. Given that the brain and spinal cord are the principal therapeutic targets of analgesics and anesthetics, this deficiency in clinical care is even more alarming. Organs that are notoriously hard to repair or replace after damage have, up until now, received comparatively little attention. In this article, a succinct overview of five neurological complications associated with surgery and anesthesia is presented. After critically reviewing the literature on the subject, the article is focused to common (delirium), controversial (postoperative cognitive decline), and potentially catastrophic (stroke, spinal cord ischemia, or postoperative visual loss) adverse events in the neurological surgery setting. The findings will increase awareness of major neurological complications to the involved surgical and anesthesia team and enhance preventive and treatment strategies during the perioperative period.
PubMed: 38947250
DOI: No ID Found -
Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis.MedRxiv : the Preprint Server For... Jun 2024Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that...
Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months in otherwise healthy individuals is not well understood, resulting in a lack of effective treatments. To address this gap, we identified the most salient physical and psychosocial consequences of debilitating sound-induced pain and reviewed the interventions that sufferers have sought for pain relief to gain insights into the underlying mechanisms of the condition. Adults ( = 32) with pain hyperacusis attended a virtual focus group to describe their sound-induced pain. They completed three surveys to identify common symptoms and themes that defined their condition and to describe their use of pharmaceutical and non-pharmaceutical therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) that occurs either in the ear or elsewhere in the body (i.e., referred pain). Participants reported using numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms of pain hyperacusis and therapeutic approaches are largely consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models is needed to identify, validate, and treat the pathological mechanisms of pain hyperacusis.
PubMed: 38946957
DOI: 10.1101/2024.06.19.24309185 -
Analytical Cellular Pathology... 2024Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays...
BACKGROUND
Biliary atresia (BA) is a devastating congenital disease characterized by inflammation and progressive liver fibrosis. Activation of hepatic stellate cells (HSCs) plays a central role in the pathogenesis of hepatic fibrosis. Our study aimed to investigate the pharmacological effect and potential mechanism of pirfenidone (PFD) and andrographolide (AGP) separately and together on liver fibrosis of BA.
MATERIALS AND METHODS
The bile ducts of male C57BL/6J mice were ligated or had the sham operation. The effects of PFD and/or AGP on liver fibrosis of BA were evaluated. Human hepatic stellate cells (LX-2) were also treated with PFD and/or AGP .
RESULTS
PFD and/or AGP ameliorates liver fibrosis and inflammation in the mice model of BA, as evidenced by significant downregulated in the accumulation of collagen fibers, hepatic fibrosis markers (-SMA, collagen I, and collagen IV), and inflammatory markers (IL-1, IL-6, and TNF-). Moreover, compared with monotherapy, these changes are more obvious in the combined treatment of PFD and AGP. Consistent with animal experiments, hepatic fibrosis markers (-SMA, collagen I, and CTGF) and inflammatory markers (IL-1, IL-6, and TNF-) were significantly decreased in activated LX-2 cells after PFD and/or AGP treatment. In addition, PFD and/or AGP inhibited the activation of HSCs by blocking the TGF-/Smad signaling pathway, and the combined treatment of PFD and AGP synergistically inhibited the phosphorylation of Smad2 and Smad3.
CONCLUSION
The combined application of PFD and AGP exerted superior inhibitive effects on HSC activation and liver fibrosis by mediating the TGF-/Smad signaling pathway as compared to monotherapy. Therefore, the combination of PFD and AGP may be a promising treatment strategy for liver fibrosis in BA.
Topics: Hepatic Stellate Cells; Animals; Liver Cirrhosis; Signal Transduction; Diterpenes; Male; Transforming Growth Factor beta; Mice, Inbred C57BL; Smad Proteins; Humans; Pyridones; Cell Line; Mice; Biliary Atresia; Disease Models, Animal; Drug Therapy, Combination
PubMed: 38946862
DOI: 10.1155/2024/2751280