Pain Conditions Research Articles

Evolution and characteristics of nocturnal knee pain after knee arthroplasty.

Nocturnal knee pain and sleep disorders are two common but poorly studied issues contributing to dissatisfaction following knee arthroplasty. This study aims to evaluate the prevalence and associated factors of nocturnal pain and sleep disturbance in a population undergoing knee arthroplasty. We included in this prospective observational study 111 patients undergoing knee athroplasty (79 TKA and 32 UKA). Sleep quality, nocturnal knee pain (preoperatively, at day 3, at 3 and 6 weeks, at 3 months and one year after surgery), pain during mobilization and neuropathic pain were evaluated by scores. Painkillers and sleeping pills intake were recorded. Potentially predictive factors for postoperative nocturnal pain evolution were studied. Poor sleeping quality rate was 54% for the pre-operative patients and was still 53% at one year after surgery. The prevalence of nocturnal knee pain was 38,74% before surgery and 2,9% at one year after arthroplasty. This study has been performed at the University Hospital Saint Luc Brussels. Evolution and Characteristics of nocturnal knee pain after knee arthroplasty. Nocturnal pain after knee surgery was significantly associated with higher pain scores at rest during activity and at night. Nocturnal pain was significantly associated with a higher PSQI and DN4 scores and a higher consumption of painkillers or sleeping pills at W6. The multiple variable regression showed a statistically significant correlation between preoperative and postoperative nocturnal pain at D3 and W3. Compared to TKA, UKA patients reported significantly less nocturnal pain at W3 and W6. Bad sleeping quality is present in 54% of knee arthroplasty patients before and after surgery. Nocturnal pain is present in 39% of knee arthroplasty patients before surgery and this drops to 3% after one year. Nocturnal pain is associated with higher pain intensity, neuropathic symptoms, increased medication consumption and poor sleeping quality. Night pain disappeared faster after UKA than TKA, with a tipping point around 6 weeks postoperatively.

Chronic shoulder pain due to spinal accessory nerve palsies present opportunities for improved care integration.

Aim: Chronic shoulder pain due to iatrogenic spinal accessory nerve (SAN) injury continues to be under-recognized, resulting in delayed time-to-diagnosis and poorer outcomes. Solutions are needed to improve the management of this condition, which can be challenging as care needs to be coordinated across pain management, neurophysiology, rehabilitationand reconstructive surgery.Cases: We present a series of sixpatients with shoulder pain refractory to conservative pain treatments to highlight how SAN injuries continued to be missed and treatment delayed, even at advanced care centers. The time to diagnosis of SAN palsy took an average of 21months and treatment was inconsistent for all patients.Discussion: None of the sixcases had initial suspicion of SAN palsy and only onepatient received targeted SAN injury care. SAN treatment should be started as early as possible so that patients can be referred for prompt surgical evaluation if they fail conservative management. Integrated care pathways may be a solution for formalizing multidisciplinary team involvement and improving SAN injury outcomes.Conclusion: Systemic processes, such as integrated care pathways, are needed to optimize early recognition and targeted treatment of SAN injury and may be beneficial for other underdiagnosed and undertreated neuropathic pain conditions.

Development and external validation of a novel modality for rapid recognition of aortic dissection based on peripheral pulse oximetry waveforms.

Aortic dissection (AD) is a life-threatening cardiovascular emergency that is often misdiagnosed as other chest pain conditions. Physiologically, AD may cause abnormalities in peripheral blood flow, which can be detected using pulse oximetry waveforms. This study aimed to assess the feasibility of identifying AD based on pulse oximetry waveforms and to highlight the key waveform features that play a crucial role in this diagnostic method. This prospective study employed high-risk chest pain cohorts from two emergency departments. The initial cohort was enriched with AD patients (n=258, 47% AD) for model development, while the second cohort consisted of chest pain patients awaiting angiography (n=71, 25% AD) and was used for external validation. Pulse oximetry waveforms from the four extremities were collected for each patient. After data preprocessing, a recognition model based on the random forest algorithm was trained using patients' gender, age, and waveform difference features extracted from the pulse oximetry waveforms. The performance of the model was evaluated using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA). The importance of features was also assessed using Shapley Value and Gini importance. The model demonstrated strong performance in identifying AD in both the training and external validation sets. In the training set, the model achieved an area under the ROC curve of 0.979 (95% CI: 0.961-0.990), sensitivity of 0.918 (95% CI: 0.873-0.955), specificity of 0.949 (95% CI: 0.912-0.985), and accuracy of 0.933 (95% CI: 0.904-0.959). In the external validation set, the model attained an area under the ROC curve of 0.855 (95% CI: 0.720-0.965), sensitivity of 0.889 (95% CI: 0.722-1.000), specificity of 0.698 (95% CI: 0.566-0.812), and accuracy of 0.794 (95% CI: 0.672-0.878). Decision curve analysis (DCA) further showed that the model provided a substantial net benefit for identifying AD. The median mean and median variance of the four limbs' signals were the most influential features in the recognition model. This study demonstrated the feasibility and strong performance of identifying AD based on peripheral pulse oximetry waveforms in high-risk chest pain populations in the emergency setting. The findings also provided valuable insights for future human fluid dynamics simulations to elucidate the impact of AD on blood flow in greater detail.

Effect of repetitive transcranial magnetic stimulation on trigeminal-mediated headshaking in 17 horses.

Trigeminal-mediated headshaking is a neuropathic facial pain condition in horses. No treatment has been entirely successful. Repetitive transcranial magnetic stimulation (rTMS) is used in human medicine as a treatment for various neuropathic pain conditions, and good results have been achieved in cases of trigeminal neuralgia. Apply rTMS to horses with trigeminal-mediated headshaking (TMHS) and to evaluate tolerability, application of the setting, and success rate. Seventeen horses with nonseasonal signs of TMHS. Other underlying causes of headshaking were ruled out. The rTMS was performed under standing sedation on 5 consecutive days applying 3 sets of 500 stimulations each, with a stimulation strength of 5 Hz. Horses were evaluated on Day 1 (t0) and Day 5 (t1) of the treatment and 2 (t2) and 4 weeks (t3) afterwards using a special scoring system. The rTMS was well tolerated. Headshaking signs during exercise were decreased by 70% (Day 5; t1). Four weeks after rTMS, signs were still decreased (mean reduction of 50%) during exercise. Improvement of mean resting and exercise scores was significant (P < .05) and effect sizes between pretreatment and all time points after treatment (t1, t2, t3) were large (>±0.8). Repetitive transcranial magnetic stimulation may be a promising treatment for neuropathic pain and headshaking in affected horses. Pain-free periods after treatment differ individually, and repeated treatment may be necessary. More studies should be performed to determine ideal settings for horses.

Progress Toward Meaning-as-Goal and Its Association with Pain, Functioning, and Global Meaning and Purpose Among Veterans with Co-occurring Chronic Pain and PTSD.

Co-occurring chronic pain and posttraumatic stress disorder (PTSD) is associated with poorer physical and mental functioning and well-being. Treatments often incorporate goal-setting around personally meaningful behaviors; however, it is unclear whether intentionally focusing on improving meaning and purpose in life (i.e., meaning-as-goal) may also serve as a helpful treatment target. The objective of the current study is to determine whether reported progress toward meaning-as-goal at 6months is associated with pain severity and interference, physical and mental health functioning, and global meaning and purpose at 6- and 12-months. Data were collected as part of an evaluation effort focused on VA's Whole Health System implementation efforts. VA electronic health records were linked to survey data across three time points (baseline, 6months, and 12months) from Veterans with both chronic pain and PTSD across 18 VA sites. A total of 1341 Veterans met inclusion criteria (mean age = 62, SD = 11.7). Regression analyses showed that progress toward meaning-as-goal was significantly associated with all 6-month variables, with standardized coefficients ranging from - 0.14 (pain severity and interference) to .37 (global meaning and purpose), in addition to all 12-month variables, with standardized coefficients ranging from - .13 (pain severity and interference) to .31 (global meaning and purpose). Efforts to intentionally promote meaning and purpose as part of evidence-based treatment for chronic pain and PTSD may lead to decreased pain and improved physical and mental health functioning and global meaning and purpose. With coefficients ranging from small to moderate effect sizes, more work is needed to better understand how best to maximize meaning-related goals.

Safety analysis of fluoroquinolone drugs in elderly patients over 65 based on FAERS

ABSTRACT Objective This study investigates adverse drug event (ADE) reports from the FAERS related to FQs drugs (ciprofloxacin, levofloxacin, moxifloxacin, and ofloxacin) in patients aged 65 and older. The findings aim to guide the rational clinical use of these drugs in elderly patients. Methods We employed Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) methods to analyze ADE reports for the representative FQ drugs from Q1 2015 to Q4 2023, covering 36 quarters. Results The analysis identified 6883 ADE cases for ciprofloxacin, 5866 for levofloxacin, 1498 for moxifloxacin, and 317 for ofloxacin. Moxifloxacin showed higher incidences of Cardiac disorders and Psychiatric disorders ADEs (4.01%, 23.11%).The strongly associated ADEs were Torsade de pointes(X2:255.69),Delirium(X2:4600.04),Dysphoria(X2:11802.38),Mental disorder(X2:3584.69);Vascular disorders ADEs were similar among FQs.Ciprofloxacin and levofloxacin showed higher ADE rates in musculoskeletal and connective tissue diseases (20.18% and 26.97%) compared to moxifloxacin(3.62%) and ofloxacin(9.25%),The most frequently reported and strongly associated ADEs were tendinitis (X2: 13383.57, X2: 31499.01), tendon pain (X2: 18730.22, X2: 40313.79), and tendon disorders (X2: 9534.69, X2: 13143.72).Additionally, moxifloxacin and ofloxacin showed higher ADE rates for eye disorders (10.61% and 15.03%). Significant ADEs included iridocyclitis (X2: 10931.34) and corneal erosion (X2: 1348.35). Conclusion Different FQs exhibit varying ADE profiles across cardiovascular, vascular and lymphatic, renal and urinary, psychiatric, musculoskeletal and connective tissue, and ocular systems. Patients with underlying systemic diseases should avoid FQs with higher ADE risks for their conditions. Enhanced monitoring and evaluation of FQs are crucial for promptly identifying and managing adverse reactions. Personalized medication plans for elderly patients should also be strengthened.

Reducing pain by improving brain and muscle activity with motor cortical neuromodulation in women with interstitial cystitis/bladder pain syndrome: a study protocol for a randomized controlled trial

IntroductionInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic pain condition creating a wide range of urologic and pain symptoms. There is currently limited evidence to understand the mechanisms of IC/BPS. There have been recent studies suggesting that altered function in brain motor areas, particularly the supplementary motor cortex (SMA), relates to altered bladder sensorimotor control and may play an important role in IC/BPS. This study aims to provide evidence that non-invasive stimulation targeting the motor cortex may help reduce IC/BPS pain, as well as better understand the neural mechanism by which this stimulation targets neuromuscular dysfunction.This study is a two-group quadruple-blinded randomized controlled trial (RCT) of active vs. sham repetitive transmagnetic stimulation (rTMS). In addition, our study will also include functional magnetic resonance imaging (fMRI), pelvic floor electromyography (EMG), pelvic exam, and outcome measures and questionnaires to further study outcomes.Ethics and disseminationAll aspects of the study were approved by the Institutional Review Board of the University of Southern California (protocol HS-20–01021). All participants provided informed consent by the research coordinator/assistants. The results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences.Trial registrationClinicalTrials.gov NCT04734847. Registered on February 1, 2021.

Efficacy and safety of antidepressants for pain in older adults: A systematic review and meta-analysis.

In many countries, pain is the most common indication for use of antidepressants in older adults. We reviewed the evidence from randomized controlled trials on the efficacy and safety of antidepressants, compared to all alternatives for pain in older adults (aged ≥65 years). Trials published from inception to 1 February 2024, were retrieved from 13 databases. Two independent reviewers extracted data on study and participant characteristics, primary efficacy (pain scores, converted to 0-100 scale) and harms. Estimates for efficacy were pooled using a random effects model and reported as difference in means and 95% CI. Quality of included trials was assessed using the Cochrane risk of bias tool. Fifteen studies (n = 1369 participants) met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (6/15 studies each). Pain related to knee osteoarthritis was the most studied (6/15 studies). For knee osteoarthritis, antidepressants did not provide a statistically significant effect for the immediate term (0-2weeks), (-5.6, 95% confidence interval [CI]: -11.5 to 0.3), but duloxetine provided a statistically significant, albeit a very small effect in the intermediate term, (≥6weeks and <12 months), (-9.1, 95% CI: -11.8 to -6.4). Almost half (7/15) of the studies reported increased withdrawal of participants in the antidepressant treatment group vs. the comparator group due to adverse events. For most chronic painful conditions, the benefits and harms of antidepressant medicines are unclear. This evidence is predominantly from trials with sample sizes of <100, have disclosed industry ties and classified as having unclear or high risk of bias.

Pain, Substance Use Disorders, Mental Health, and Buprenorphine Treatment among Patients With and Without HIV.

Treatment of opioid use disorder (OUD) with buprenorphine improves outcomes and mortality among people with HIV (PWH). However, engagement is low and is influenced by comorbidities. We examined the impact of patterns of co-occurring pain, substance use disorders (SUDs), and mental health diagnoses on buprenorphine initiation and retention in PWH. The Veterans Aging Cohort Study contained 7,875 patients (2,702 PWH and 5,173 without HIV) with new OUD clinical encounters (2008-2017). Buprenorphine initiation and retention were derived from prescription data. We identified patterns of co-occurring diagnoses (via ICD codes) and assessed the effects of class membership on both outcomes using latent class analysis and regression analyses. The mean age of patients was 55, 98% were male, 58% Black, 8% Hispanic, and only 8% initiated buprenorphine within 12 months of OUD diagnosis. Four classes of co-occurring diagnoses were identified: "Few Co-occurring Diagnoses" (42.3%); "Multiple Pain Conditions" (21.3%); "Pain + SUD" (18.4%) and "Pain + SUD + Mental Health" (18.0%). Patients in the "Pain + SUD" class and "Pain + SUD + Mental Health" class were significantly less likely to initiate buprenorphine and had 59% and 45% lower odds, respectively, of initiating buprenorphine compared with patients in the "Few Co-occurring Diagnoses" class; this effect did not vary by HIV status. Buprenorphine retention was not significantly associated with HIV status or class membership. However, Black Veterans were less likely to initiate or be retained in buprenorphine treatment. Higher comorbidity burden was negatively associated with buprenorphine initiation but not with retention. More research is warranted to determine other factors that may influence treatment retention.

Psychometric validation of the Italian Self-Report Symptoms inventory (SRSI): Factor structure, construct validity, and diagnostic accuracy

The Self-Report Symptom Inventory (SRSI) is a novel tool designed to detect symptom overreporting and other forms of noncredible responding. Unlike existing scales, the SRSI includes genuine and pseudosymptoms scales covering cognitive, affective, motor, pain, and post-traumatic stress disorder domains. The present study aims to investigate the psychometric properties of the Italian Version of the SRSI (SRSI-It), in particular, its factor structure, reliability, convergent and discriminant validity, and diagnostic accuracy. Data from 1180 healthy participants showed a hierarchical structure with higher-order constructs for genuine symptoms and pseudosymptoms, each comprising five subscales. The SRSI-It showed a strong convergent validity with the Structured Inventory of Malingered Symptomatology and discriminant validity through low correlations with the Psychopathic Personality Inventory-Revised. Receiver operating characteristic analysis determined cut scores of 6 (95% specificity) and 9 (98% specificity) for pseudosymptoms, with a Ratio Index score of 0.289 (82% specificity). In summary, the SRSI-It appears to be a promising tool for identifying symptom exaggeration in clinical and forensic contexts, ultimately enhancing the quality and reliability of evaluations in these contexts.

Burden and Risk Factors of Cervical Spine Conditions in Military Aircrew From 1997 to 2015: A Retrospective Cohort Study.

Military aviators may have increased risk of cervical spine injuries because of exposure to supraphysiologic forces and vibration during dynamic flight. Aviator medical attrition impairs mission readiness, decreases operational capabilities, increases overall DoDcosts, and decreases retention of seasoned aviators. This study evaluated incidence and risk factors for cervical spine conditions in U.S. military aviators from 1997 to 2015. The Defense Medical Epidemiological Database was queried for aviators with a diagnosis of cervical spine conditions. Pertinent ICD-9 codes for cervical spine pathology were ascertained from U.S. Army, Air Force, and Naval Air Forces aeromedical references. Negative binomial regressions assessed sex, age, service, aircraft, and year on incidence of conditions. Rates were compared to non-aviator controls. The study was approved by the Institutional Review Board at the Naval Health Research Center (NHRC.2020.0205-NHSR). Incidence rates were 9.78 to 12.57/1,000 person-years for neck pain, 2.04 to 3.89/1,000 person-years for degenerative conditions without neurological involvement, and 0.94 to 1.36/1,000 person-years for degenerative conditions with neurological involvement. Aviation occupation (relative risk [RR] 1.41-2.05), female sex (RR 3.32-7.89), age over 40 (RR 2.39-4.62), and service in the Army or Marine Corps (RR 1.62-2.14) were risk factors. Military aviators had a statistically significant increase in risk of neck pain and medically disqualifying degenerative cervical spine conditions compared to non-aviator controls. Rates of neck pain increased in all aviators over the study epoch. Possible explanations could be related to the operational demands and the increased use of forward helmet-mounted display systems during the study period, a supposition that requires further investigation. There was no significant difference in rates of neck pain or degenerative cervical conditions between aircraft platforms (fighter/bomber, other fixed wing, and rotary wing). Female sex, age over 40 years, and Army/Marine Corps service were the greatest risk factors for neck pain and degenerative cervical spine conditions. Targeted prevention programs and expanded treatment modalities are necessary to reduce aviator attrition and Department of Defense cost burden.

Predictive Model for Opioid Use Disorder in Chronic Pain: A Development and Validation Study

Background/Objective: There are several questionnaires for the challenge of anticipating opioid use disorder (OUD). However, many are not specific for chronic non-cancer pain (CNCP) or have been developed in the American population, whose sociodemographic factors are very different from the Spanish population, leading to scarce translation into clinical practice. Thus, the aim of this study is to prospectively validate a predictive model for OUD in Spanish patients under long-term opioids. Methods: An innovative two-stage predictive model was developed from retrospective (n = 129) and non-overlapping prospective (n = 100) cohorts of real-world CNCP outpatients. All subjects used prescribed opioids for 6 or more months. Sociodemographic, clinical and pharmacological covariates were registered. Mu-opioid receptor 1 (OPRM1, A118G, rs1799971) and catechol-O-methyltransferase (COMT, G472A, rs4680) genetic variants plus cytochrome P450 2D6 (CYP2D6) liver enzyme phenotypes were also analyzed. The model performance and diagnostic accuracy were calculated. Results: The two-stage model comprised risk factors related to OUD (younger age, work disability and high daily opioid dose) and provided new useful information about other risk factors (low quality of life, OPRM-G allele and CYP2D6 extreme phenotypes). The validation showed a satisfactory accuracy (70% specificity and 75% sensitivity) for our predictive model with acceptable discrimination and goodness of fit. Conclusions: Our study presents the results of an innovative model for predicting OUD in our setting. After external validation, it could represent a change in the paradigm of opioid treatment, helping clinicians to better identify and manage the risks and reduce the side effects and complications.

Feasibility of a Virtual Adaptation of a Yoga Intervention for Veterans with Chronic Pain and Posttraumatic Stress Disorder.

Purpose/Objective: This study assessed the feasibility and acceptability of a yoga intervention for veterans with comorbid posttraumatic stress disorder (PTSD) and chronic pain (CP) that was adapted for virtual implementation. Research Method/Design: This pilot feasibility study at a large, mid-Atlantic Veteran's Affairs (VA) Medical Center with veterans with both PTSD and CP examined the adaptation of an eight-session virtual yoga group intervention. Participants (n = 18, 11 completers) were primarily male (82.4%), African American (76.5%), with no prior yoga experience (70.6%). A measure of client satisfaction was administered at completion and attendance rates were examined. Self-reported symptom measures were also assessed. Results: There were no instances of injuries or other adverse effects related to the study. This study yielded a 39% attrition rate, consistent with in-person yoga interventions. Mean number of sessions attended was 5.53 (SD = 1.73). Participants rated overall satisfaction as high (M = 28.09; SD = 3.96; potential range 8-32). Conclusions/Implications: This study provides initial data on the acceptability of a virtual yoga intervention for veterans with comorbid PTSD and CP, with attrition and satisfaction rates in line with prior in-person iterations. Implications of virtual adaption and considerations for future efforts will be discussed. This study was not preregistered but has been registered subsequently on ClinicalTrials.gov [CTR #: NCT06123065].

Does diagnosis matter? Evaluating impact of pediatric chronic pain diagnosis on pain and function.

This study aimed to A) evaluate changes in pain and function following an outpatient interdisciplinary pain management program (IPMP) for children with different chronic pain conditions and B) explore differences in pain and function at baseline and discharge for different diagnoses. A retrospective chart review was performed for 488 children who participated in an outpatient IPMP. Children's pain and physical, social, and emotional functioning were assessed at initial evaluation, discharge, and one-to-two-month follow-up. Patients were stratified by diagnosis (complex regional pain syndrome [CRPS], headache, musculoskeletal pain, visceral pain, and widespread pain) to evaluate differences in pain and functioning at baseline and discharge. Children's pain and function improved from initial evaluation to discharge. Those with headache and musculoskeletal pain exhibited better baseline physical and emotional functioning than other diagnostic groups (p = 0.03; p = 0.005; p = 0.002; p = 0.04). Children with CRPS displayed the worst baseline physical functioning (p = 0.003). Those with widespread pain exhibited the worst baseline emotional functioning at both initial evaluation and discharge (p = 0.009; p = 0.007). Children with CRPS, visceral pain, and widespread pain undergoing treatment in an IPMP exhibited the most impaired baseline functioning, while those with musculoskeletal pain and headache were least impaired. All exhibited improvements in pain and function following the IPMP.

Microbiome contributions to pain: a review of the preclinical literature.

Over the past 2 decades, the microbiome has received increasing attention for the role that it plays in health and disease. Historically, the gut microbiome was of particular interest to pain scientists studying nociplastic visceral pain conditions given the anatomical juxtaposition of these microorganisms and the neuroimmune networks that drive pain in such diseases. More recently, microbiomes both inside and across the surface of the body have been recognized for driving sensory symptoms in a broader set of diseases. Microbiomes have never been a more popular topic in pain research, but to date, there has not been a systematic review of the preclinical microbiome pain literature. In this article, we identified all animal studies in which both the microbiome was manipulated and pain behaviors were measured. Our analysis included 303 unique experiments across 97 articles. Microbiome manipulation methods and behavioral outcomes were recorded for each experiment so that field-wide trends could be quantified and reported. This review specifically details the animal species, injury models, behavior measures, and microbiome manipulations used in preclinical pain research. From this analysis, we were also able to conclude how manipulations of the microbiome alter pain thresholds in naïve animals and persistent pain intensity and duration in cutaneous and visceral pain models. This review summarizes by identifying existing gaps in the literature and providing recommendations for how to best plan, implement, and interpret data collected in preclinical microbiome pain experiments.

Nationally Representative Rates of Incident Prescription Opioid Use Among United States Adults and Selected Subpopulations: Longitudinal Cohort Study from the National Health Interview Survey, 2019-2020

Nationally representative rates of incident prescription opioid use in the United States (U.S.) adult population and selected subpopulations are unknown. Using the National Health Interview Survey (2019-2020) longitudinal cohort, a cohort with 1-year follow-up created using random cluster probability sampling of non-institutionalized civilian U.S. adults, we estimated rates and predictors of incident opioid use. Of 21,161 baseline (2019) participants randomly chosen for follow-up, the final analytic sample included 10,415 who also participated in 2020. Exposure variables were selected per the socio-behavioral model of healthcare utilization: predisposing characteristics (sex, age, race, etc.), enabling characteristics (socioeconomic status, insurance status), health status (pain, disability, comorbidities, etc.), and healthcare use (office visits, emergency room [ER] visits, hospitalizations). Among adults who did not use prescription opioids in 2019, a one-year cumulative incidence of 4.1% (95% CI:3.5-4.6) was seen in 2020, with an incidence rate (IR) of 32.6 cases of new prescription opioid use per 1,000 person-years (PY). Cumulative incidence, IR, and adjusted relative risk (RR) varied by participant characteristics. We observed the highest IR in those with ineffective pain treatment (81.6 cases per 1,000 PY) and those who visited the ER ≥3 times (93.8 cases per 1,000 PY). Participants reporting ≥4 painful conditions had an adjusted RR of 2.9 (95% CI:2.0-4.1), while the RR for those with sleep problems was 2.3 (95% CI:1.7-3.1). Overall, this study presents nationally representative rates of incident prescription opioid use, and suggests that some participants are using prescription opioids as an early resort analgesic contrary to best practice guidelines. PerspectiveThis longitudinal cohort study presents nationally representative rates of incident prescription opioid use in U.S. adults and selected subpopulations. Our data suggest that some participants are using prescription opioids as a first-line or early resort analgesic, contrary to best practice guidelines.

Real World Evidence of User Experience with Microenemas for Relief of Constipation.

Constipation is a commonly reported gastrointestinal complaint. Research on this widespread condition focuses mainly on clinical trials for chronic constipation with less emphasis on patient experience and nonchronic situations. Sufferers report that constipation interferes with daily activities and quality of life. It is likely that this is common among all sufferers of constipation, regardless of how often the condition is experienced. This work explored attitudes and perceptions of people who experience occasional constipation and self-treat with over the counter products, particularly Microlax® microenemas. In this retrospective study, real-world data were collected from 1635 respondents from France and Russia who experienced occasional constipation. Participants completed a questionnaire about their experiences with occasional (not chronic) constipation and perceptions of over the counter treatments of oral laxatives, suppositories, and Microlax microenemas. Questions focused on comfort, quality of life, ease of use, and reliability of these treatments. Participants had used the microenema for treatment of occasional constipation within 3 months of study participation. Occasional constipation was based on the Rome IV diagnostic criteria for adults and babies. Data were analyzed across the total population of all groups, then by subgroup. Success criteria were defined as of at least 70% agreement with the statements scoring ≥ 7 on the scale of 0-10. The proportion of respondents agreeing with the individual statements was calculated using the denominator for the total sample within each group. This study shows that experiencing even occasional bouts of constipation negatively affect quality of life and well-being. Participants (women aged 25-54 years, older men, and women aged 60-80 years) reported that it severely limited daily life and activities and caused negative emotions and embarrassment. Pregnant women and mothers with babies showed great concern that constipation indicated a serious and painful condition and was bad for their babies. Participants agreed that using Microlax microenema provided greater ease of use, comfort, reliability, and safety than oral laxatives and rectal suppositories. Sufferers of occasional constipation report that these bouts interfere with their daily lives and reduce quality of life, similar to what is reported for those with chronic constipation based on existing literature. The microenema, Microlax, showed benefits in the relief of occasional constipation compared with oral laxatives and rectal suppositories. Trepidation about using the microenema, experienced before using it, was greatly reduced after the first and subsequent uses. Microlax microenema enabled users to regain the feeling of control and provided positive impacts on quality of life and well-being.

Supraclavicular Brachial Plexus Block with and without Dexamethasone as Local Anaesthetics

Background: Brachial plexus block is good alternative to general anesthesia for upper limb surgery. This avoids the unwanted effect of anesthetic drugs used during general anesthesia and the stress of upper airway instrumentation. Peripheral nerve blocks can be used for anesthesia, postoperative analgesia, diagnosis and treatment of chronic pain disorders. This study was carried out to compare onset and duration of sensory and motor blockade and duration of postoperative analgesia on addition of dexamethasone to local anestheic and local anesthetic alone in supraclavicular brachial plexus block. Methods: In this prospective randomized, controlled, double blinded study which was conducted at Department of Anesthesia, 250 Beded Hospital, Lalmonirhat, Rangpur, Bangladesh from January to June 2023. We included 70 ASA I &amp; II patients who were aged between 18 years &amp; 60 years, underwent elective upper limb surgeries. They were divided into two equal groups. Group 1 (cases) who received 15 milliliter of 2% lignocaine with adrenaline and 15 milliliter of 0.5% bupivacaine + dexamethasone 8mg (2ml). Group 2 (controls) who received 15 milliliter of 2% lignocaine with adrenaline and 15 milliliter of 0.5% bupivacaine + 0.9% normal saline (2ml). We observed the Onset of sensory and motor blockade, duration of sensory and motor blockade and postoperative analgesia between the two groups. Results: In this study of patients according to their age and weight. 37.26±15.55 years were mean age in group 1 and in group 2 it was 36.56±16.86 with p value being 0.8678. 58.466± 3.9642 kg was the mean weight in group 1 and in group 2 it was 60.4±4.95 kg with p value of 0.1002. So both the groups were comparable in terms of age and weight. In this study out of 70 patients, group1 consisted of 68.6% males whereas there were 60% in group 2 and group 1consisted of 31.4% of females and 40% in group2, hence males’ outnumbered females in both the groups. The mean duration of surgery in group 1 was 50±19.95 minutes and in group 2 were 46.6±15.55 minutes with p value of 0.4646. There was no statistical difference between both the groups. The onset of sensory blockade was within 7.3 min in group 1. In group 2 the onset of sensory blockade was 13.66 minutes. The onset of motor blockade was within 3.93 min in group 1. In group 2 the onset of motor blockade was 18.66 min. The duration of intra operative analgesia was 654.33 minutes in group 1. In group 2 the duration of intra operative analgesia was 292.6 minutes. The duration of post-operative analgesia was 815±13.57 minutes in group 1. The duration of post-operative analgesia in group 2 was 393.8±42.88 minutes. There were no complications in both the groups in intra operative period and post-operative period. Conclusion: Dexamethasone, when added to 15 millilitre of 0.5% bupivacaine and 15 millilitre of 2% lignocaine plus adrenaline, very effectively enhances the onset of sensory and motor blockade. It dramatically prolongs the duration of sensory and motor blockade and duration of analgesia. There were no untoward side effects with the use of dexamethasone as an additive in the brachial plexus block.

Neuromolecular and behavioral effects of Cannabidiol on depressive-associated behaviors and neuropathic pain conditions in mice

Neuropathic pain (NP) has a high incidence in the general population, is closely related to anxiety disorders, and has a negative impact on the quality of life. Cannabidiol (CBD), as a natural product, has been extensively studied for its potential therapeutic effects on symptoms such as pain and depression (DP). However, the mechanism of CBD in improving NP with depression is not fully understood. First, we used bioinformatics tools to deeply mine the intersection genes associated with NP, DP, and CBD. Secondly, the core targets were screened by Protein-protein interaction network, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, molecular docking and molecular dynamics simulation. Next, the effects of CBD intervention on pain and depressive behaviors in the spinal nerve ligation (SNL) mouse model were evaluated using behavioral tests, and dose-response curves were plotted. After the optimal intervention dose was determined, the core targets were verified by Western blot (WB) and Quantitative Polymerase Chain Reaction (qPCR). Finally, we investigated the potential mechanism of CBD by Nissl staining, Immunofluorescence (IF) and Transmission Electron Microscopy (TEM). A total of five core genes of CBD most associated with NP and DP were screened by bioinformatics analysis, including PTGS2, GPR55, SOD1, CYP1A2 and NQO1. Behavioral test results showed that CBD by intraperitoneal administration 5mg/kg can significantly improve the pain behavior and depressive state of SNL mice. WB, qPCR, IF, and TEM experiments further confirmed the regulatory effects of CBD on key molecules. In this study, we found five targets of CBD in the treatment of NP with DP. These findings provide further theoretical and experimental basis for CBD as a potential therapeutic agent.

The gut microbiome and the brain.

The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions. The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function. Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions.