Chronic Pain Disorders Research Articles

Hacking the Predictive Mind.

According to active inference, constantly running prediction engines in our brain play a large role in delivering all human experience. These predictions help deliver everything we see, hear, touch, and feel. In this paper, I pursue one apparent consequence of this increasingly well-supported view. Given the constant influence of hidden predictions on human experience, can we leverage the power of prediction in the service of human flourishing? Can we learn to hack our own predictive regimes in ways that better serve our needs and purposes? Asking this question rapidly reveals a landscape that is at once familiar and new. It is also challenging, suggesting important questions about scope and dangers while casting further doubt (as if any was needed) on old assumptions about a firm mind/body divide. I review a range of possible hacks, starting with the careful use of placebos, moving on to look at chronic pain and functional disorders, and ending with some speculations concerning the complex role of genetic influences on the predictive brain.

Chronic health conditions and disability are prevalent among community users of a digital mental health service: a scoping survey

Objectives: Digital interventions can offer accessible and scalable treatment for chronic conditions, though often focus separately on physical or mental health. People accessing digital health services may live with multiple conditions or experience overlapping symptoms. This study aimed to describe the breadth and characteristics of chronic health conditions and self-reported disability among routine users of a digital mental health service, and to examine related motivations to engage with digital mental health interventions. Methods: A cross-sectional survey of adults registered with a digital mental health service in the Australian community (THIS WAY UP) was conducted. Participant demography, chronic health conditions, self-reported disability and motivations for accessing digital treatment were collected and analyzed descriptively. Results: 366 participants responded (77% female, mean age 50 ± 15 years). 71.6% of participants (242/338) reported ≥1 chronic health condition and one-third reported multimorbidity (112/338, 33.1%). Chronic pain, musculoskeletal and connective tissue disorders were most common. 26.9% of respondents (90/334) reported a disability, most commonly physical disabilities. 95% of those with chronic conditions reported negative mental health effects and 46% reported heightened interest in digital mental health treatments because of their condition. Primary motivations for digital service use were receiving a recommendation from a health professional and service accessibility. Discussion: People who access digital mental health services in routine care report high rates of heterogenous chronic illness and related disability. There is interest in accessible digital treatments to support mental health at scale among people who live with varied chronic conditions and disabilities.

Multimodal pain therapy for patients with endometriosis: care structure in German pain centres

It is estimated that every tenth woman of childbearing age has endometriosis. That's around 1.7 million sufferers in Germany. There are around 40,000 new diagnoses every year (Diedrich et al. 2006). The most important leading symptom is severe pain during menstruation, but also abdominal pain independent of the period. The more severe the pain, the greater the reduction in quality of life (Facchin et al. 2015). Depending on the localisation of endometriosis lesions, other symptoms, functional complaints and accompanying symptoms may also occur. Endometriosis is a chronic pain disorder that often takes several years to be diagnosed. In addition, current therapies result in high recurrence rates and the cause of the disease remains unclear (Diedrich et al. 2006; AWMF 2020). The long-lasting pain leads to complex neurological changes that often cause the pain to become chronic (Ball and Khan 2020; Brawn et al. 2014). Pain is defined as chronic if it lasts for more than three months or is recurrent (Treede et al. 2019).

Yoga and Physical Therapy for Chronic Pain and Opioid Use Disorder Onsite in an Opioid Treatment Program: A Randomized Controlled Trial.

There is a lack of integrated treatment for chronic pain and opioid use disorder (OUD). Yoga and physical therapy (PT) may improve pain and physical function of people living with (PLW) chronic low back pain (CLBP) and may also reduce opioid craving and use, but PLW with OUD face barriers to accessing these interventions. We hypothesize that compared to treatment as usual (TAU), providing yoga and PT onsite at opioid treatment programs (OTPs) will be effective at improving pain, opioid use, and quality of life among people with CLBP and OUD, and will be cost-effective. In this hybrid type-1 effectiveness-implementation study, we will randomly assign 345 PLW CLBP and OUD from OTPs in the Bronx, NY, to 12 weeks of onsite yoga, onsite PT, or TAU. Primary outcomes are pain intensity, opioid use, and cost-effectiveness. Secondary outcomes include physical function and overall well-being. This trial tests an innovative, patient-centered approach to combined management for pain and OUD in real-world settings. We rigorously examine the efficacy of yoga and PT onsite at OTPs as nonpharmacologic, cost-effective treatments among people with CLBP and OUD who face barriers to integrated care.

Study Protocol for the Opioid and Pain Treatment in Indigenous Communities Trial: A Systems Level Intervention for Enhanced Screening and Brief Intervention and Referral for Co-Occurring Chronic Pain and Opioid Use Disorder.

American Indian/Alaska Native (AI/AN) individuals have the highest rates of opioid overdose mortality and chronic pain (CP) compared to other racial/ethnic groups in the United States. These individuals also report higher rates of pain anxiety and pain catastrophizing, which are both associated with poorer outcomes and risk for opioid misuse (OM) and opioid use disorder (OUD) among individuals with CP. Yet, no prior studies have examined rates of comorbid pain and OUD among AI/AN adults. This commentary describes an implementation research partnership of 3 AI/AN-serving clinics and a university team that utilizes an implementation hybrid type III design to examine the impact of implementation strategies on adoption and sustainability of evidence-based screening and brief intervention for CP and OM/OUD among AI/AN clients. As part of our community-engaged approach, we embrace both AI/AN models and Western models, and a collaborative board of 10 individuals guided the research throughout. We hypothesize that our culturally centered approach will increase rates of screening and brief intervention and improve identification of and outcomes among AI/AN clients with CP and OUD who receive treatment at participating sites. Each site convenes a workgroup to evaluate and set goals to culturally center screening and brief interventions for CP and OM/OUD. Data collected include deidentified electronic health records to track screening and brief interventions and rates of CP and OUD; provider and staff surveys beginning prior to implementation and every 6 months for 2 years; and a subset of clients will be recruited (N = 225) and assessed at baseline, 6, and 12 months to examine biopsychosocial and spiritual factors and their experiences with culturally centered screening and brief intervention. Cultural adaptations to the measures and screening and brief intervention as well as barriers and facilitators will be addressed. Recommendations for successful Tribal health clinic-university partnerships are offered.

Investigation of Anti-inflammatory and Antioxidant Activities of Promising 1,4,5-Trisubstituted Pyrazoles Derivatives of Chalcone Ditosylates

Patients suffering from chronic pain and inflammatory disorders need novel COX-2 inhibitors to be developed with minimum toxicity to the kidneys, heart, and gastrointestinal tract and with excellent anti-inflammatory activity. The current study centers on an array of 1,4,5-trisubstituted pyrazoles produced via the reaction of ditosylates of chalcones with hydrochloride salt of phenylhydrazine. Chalcone was reacted with HTIB to produce a variety of derivatives of α, β chalcone ditosylates. Phenylhydrazine hydrochloride treatment of these chalcone ditosylates produced distinct 1,4,5-trisubstituted pyrazoles. The conversion process is mediated by 1,2-aryl migrations. IR, 1NMR, and elemental analysis were used to characterize the compounds after they had been purified by recrystallization. Using ascorbic acid as a reference, the DPPH (1,1-diphenyl-2-picrylhydrazyl) technique was used to assess the compounds' in vitro antioxidant activity. The paw edema technique caused by Carrageenan was utilized to assess the compounds' in vivo anti-inflammatory properties. The standard medication used was diclofenac sodium. A plethysmograph was used to measure the volume of the rats' paws. When compared to the standard, the compounds V5D5PH5 and V7D7PH7 showed modest antioxidant activity. When the synthetic pyrazoles were examined for their in vivo anti-inflammatory properties, substances V4D4PH4 and V7D7PH7 outperformed the reference. Here, we attempted to create new, safe, and effective drugs for the treatment of inflammatory disorders and pain by utilizing synthetic pyrazole moiety derivatives. Simple experimentation is used in the proposed study to improve pharmacological activity and yields. In the near future, chalcone ditosylate derivatives will be a powerful tool for selective modification.

Clinical Characteristics of Patients with Primary and Secondary Fibromyalgia in Bulgaria

Fibromyalgia (FM) is characterized by a chronic widespread pain, general fatigue, anxiety, depression, sleep disturbances and functional disorders. FM affects both women and men in 9:1 to 20:1 ratio. The purpose of this clinical study is to analyze clinical manifestations in patients with primary and secondary fibromyalgia. Eighty-three patients with primary FM, 39 patients with FM and osteoarthritis (OA), 23 patients with FM and systemic lupus erythematosus (SLE), 27 patients with SLE, and 36 healthy subjects were included. The present study compared chronic pain, fatigue, depression and anxiety in patients with primary FM, patients with SLE, FM + OA, FM + SLE and healthy subjects. Based on the 2016 criteria for number of chronic widespread pain areas, there is a statistically significant difference of the control group compared to the patients with primary FM (p = 0.001), FM + OA (p = 0.001), FM + SLE (p = 0.001), SLE (p = 0.001). Based on the MFIS fatigue scale, the chronic fatigue is a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.004), FM + OA (p = 0.02), FM + SLE (p = 0.001). Based on the HADS clinical parameter, anxiety and depression are a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.01), FM + OA (p = 0.01), FM + SLE (p = 0.01), and no difference in patients with SLE (p = 0.77). The comparison between the patient groups is important to evaluate the disease activity and the treatment to be recommended.

The associations of chronic pain and 24-h movement behaviors with incident mental disorders: evidence from a large-scale cohort study

BackgroundChronic pain was associated with a higher risk of mental disorders (e.g., depression and anxiety). However, the role of 24-h movement behaviors in the association remains unclear.MethodsA total of 72,800 participants with accelerometer data and free of mental disorders from the UK Biobank were analyzed. The compositional mediation model and isotemporal substitution model were used to explore the associations between chronic pain, 24-h movement behaviors, and the incidence of overall mental disorders, depression, and anxiety.ResultsWith a median follow-up of 13.36 years, participants with chronic pain had a higher rate of incident overall mental disorders (hazard ratio (HR): 1.281, 95% confidence interval (CI): 1.219 to 1.344), anxiety (HR: 1.391, 95% CI: 1.280 to 1.536), and depression (HR: 1.703, 95% CI: 1.551 to 1.871). Increased sedentary behavior (SB) and reduced moderate-to-vigorous physical activity (MVPA) caused by chronic pain both increased the risk of mental disorders. Twenty-four-hour movement behaviors explained the relationship between chronic pain and overall mental disorders, depression, and anxiety by 10.77%, 5.70%, and 6.86%, respectively. Interaction effects were found between MVPA and chronic pain when predicting the incidence of depression and between MVPA, sleep (SLP), and chronic pain when predicting the incidence of mental disorders. People with chronic pain would recommend at least 0.5 h per day of MVPA and 7 h per day of SLP and restricting SB below 11.5 h per day.ConclusionsTwenty-four-hour movement behaviors played a significant mediating role in the association between chronic pain and mental disorders. Individuals with chronic pain should engage in more MVPA, less sedentary behavior, and have 7-h sleep per day.

Low-Dose Buprenorphine Initiation for Hospitalized Patients With Chronic Pain and Opioid Use Disorder or Opioid Misuse: Protocol for an Open-Label, Parallel-Group, Effectiveness-Implementation Randomized Controlled Trial.

Buprenorphine is an effective medication for both opioid use disorder (OUD) and chronic pain (CP), but transitioning from full opioid agonists to buprenorphine, a partial opioid agonist, can be challenging. Preliminary studies suggest that low-dose buprenorphine initiation can overcome some challenges in starting treatment, but no randomized controlled trials have compared low-dose and standard buprenorphine initiation approaches regarding effectiveness and safety or examined implementation in hospital settings. In a pragmatic open-label hybrid type I effectiveness-implementation trial based in a single urban health system, 270 hospitalized patients with (a) CP and (b) OUD or opioid misuse are being randomized to buprenorphine treatment initiation using 5-day low-dose or standard initiation protocols. Outcomes include buprenorphine treatment uptake (primary), defined as receiving buprenorphine treatment 7 days after enrollment, and other OUD and pain outcomes at 1-, 3-, and 6-month follow-up (secondary). Data collection will also include safety measures, implementation of low-dose initiation protocols, patient acceptability, and cost-effectiveness. Comparing strategies in a randomized clinical trial will provide the most definitive data to date regarding the effectiveness and safety of low-dose buprenorphine initiation. The study will also provide important data on treating CP at a time that clinical guidelines are evolving to center buprenorphine as a preferred opioid for CP.

Rates and determinants of breastfeeding initiation in women with and without epilepsy: A 25-year study

PurposeTo examine the rates and determinants of breastfeeding initiation (BFI) amongst women with epilepsy (WWE) and women without epilepsy (WWoE) in Manitoba, Canada. MethodsWe conducted a retrospective cohort study using province-wide health databases from 1995 to 2019. Annual BFI rates for WWE and WWoE were examined. Multivariable logistic regression models were used to quantify the association between maternal and infant characteristics and BFI in both groups. ResultsDuring the study period, 1,331 pregnant WWE and 357,334 WWoE were examined. Among WWE, 70.9 % initiated breastfeeding compared to 81.8 % among WWoE. We observed a significant small increase in yearly trends of BFI in both WWE (β=0.45, p = 0.008) and WWoE (β=0.23, p < 0.001). In WWE, BFI was associated with caesarean delivery (aOR=0.72,95 % CI: 0.53–0.97), chronic pain (aOR=0.67,95 % Cl: 0.46–0.97), lower income (aOR=0.34,95 % Cl: 0.26–0.44), and gestational age (aOR= 1.09,95 % CI:1.01–1.18). In WWoE, BFI was associated with chronic pain (aOR=0.83,95 % Cl: 0.80–0.86), lower income (aOR=0.45, 95 %CI:0.44–0.46), mood and anxiety disorder (aOR=0.84,95 % CI:0.81–0.86), and gestational age (aOR=1.13,95 % Cl:1.12–1.14). The use of any ASM (aOR=0.66,95 % Cl:0.51–0.85), new generation (aOR=0.86,95 % Cl: 0.62–1.20), polytherapy (aOR=0.46,95 % Cl: 0.31–0.69) and gabapentin (aOR=0.49,95 % Cl: 0.17–1.24) reduced the likelihood of BFI among WWE. ConclusionBFI was approximately 10 % lower in WWE compared to WWoE. Determinants such as low income, ASM use, and comorbidities were significant contributors to a reduced BFI in both groups. Targeted counselling for WWE on breastfeeding benefits is essential. Further research is needed to investigate breastfeeding continuation in WWE.

The role of spinal cord neuroanatomy in the variances of epidural spinal recordings

BackgroundSpinal cord stimulation (SCS) has demonstrated multiple benefits in treating chronic pain and other clinical disorders related to sensorimotor dysfunctions. However, the underlying mechanisms are still not fully understood, including how electrode placement in relation to the spinal cord neuroanatomy influences epidural spinal recordings (ESRs). To characterize this relationship, this study utilized stimulation applied at various anatomical sections of the spinal column, including at levels of the intervertebral disc and regions correlating to the dorsal root entry zone.MethodTwo electrode arrays were surgically implanted into the dorsal epidural space of the swine. The stimulation leads were positioned such that the caudal-most electrode contact was at the level of a thoracic intervertebral segment. Intraoperative cone beam computed tomography (CBCT) images were utilized to precisely determine the location of the epidural leads relative to the spinal column. High-resolution microCT imaging and 3D-model reconstructions of the explanted spinal cord illustrated precise positioning and dimensions of the epidural leads in relation to the surrounding neuroanatomy, including the spinal rootlets of the dorsal and ventral columns of the spinal cord. In a separate swine cohort, implanted epidural leads were used for SCS and recording evoked ESRs.ResultsReconstructed 3D-models of the swine spinal cord with epidural lead implants demonstrated considerable distinctions in the dimensions of a single electrode contact on a standard industry epidural stimulation lead compared to dorsal rootlets at the dorsal root entry zone (DREZ). At the intervertebral segment, it was observed that a single electrode contact may cover 20-25% of the DREZ if positioned laterally. Electrode contacts were estimated to be ~0.75 mm from the margins of the DREZ when placed at the midline. Furthermore, ventral rootlets were observed to travel in proximity and parallel to dorsal rootlets at this level prior to separation into their respective sides of the spinal cord. Cathodic stimulation at the level of the intervertebral disc, compared to an ‘off-disc’ stimulation (7 mm rostral), demonstrated considerable variations in the features of recorded ESRs, such as amplitude and shape, and evoked unintended motor activation at lower stimulation thresholds. This substantial change may be due to the influence of nearby ventral roots. To further illustrate the influence of rootlet activation vs. dorsal column activation, the stimulation lead was displaced laterally at ~2.88 mm from the midline, resulting in variances in both evoked compound action potential (ECAP) components and electromyography (EMG) components in ESRs at lower stimulation thresholds.ConclusionThe results of this study suggest that the ECAP and EMG components of recorded ESRs can vary depending on small differences in the location of the stimulating electrodes within the spinal anatomy, such as at the level of the intervertebral segment. Furthermore, the effects of sub-centimeter lateral displacement of the stimulation lead from the midline, leading to significant changes in electrophysiological metrics. The results of this pilot study reveal the importance of the small displacement of the electrodes that can cause significant changes to evoked responses SCS. These results may provide further valuable insights into the underlying mechanisms and assist in optimizing future SCS-related applications.

Incidence and risk factors of new persistent opioid use after surgery and trauma: A systematic review

BackgroundPersistent opioid use (POU) can occur with opioid use after surgery or trauma. Current systematic reviews include patients with previous exposure to opioids, meaning their findings may not be relevant to patients who are opioid naïve (i.e. Most recent exposure was from surgery or trauma). The aim of this review was to synthesise narratively the evidence relating to the incidence of, and risk factors for POU in opioid-naïve surgical or trauma patients.MethodStructured searches of Embase, Medline, CINAHL, Web of Science, and Scopus were conducted, with final search performed on the 17th of July 2023. Searches were limited to human participants to identify studies that assessed POU following hospital admission due to surgery or trauma. Search terms relating to ‘opioid’, ‘analgesics’, ‘surgery’, ‘injury’, ‘trauma’ and ‘opioid-related disorder’ were combined. The Newcastle–Ottawa Scale for cohort studies was used to assess the risk of bias for studies.ResultsIn total, 22 studies (20 surgical and two trauma) were included in the analysis. Of these, 20 studies were conducted in the United States (US). The incidence of POU for surgical patients 18 and over ranged between 3.9% to 14.0%, and for those under 18, the incidence was 2.0%. In trauma studies, the incidence was 8.1% to 10.5% among patients 18 and over. Significant risk factors identified across surgical and trauma studies in opioid-naïve patients were: higher comorbidity burden, having pre-existing mental health or chronic pain disorders, increased length of hospital stay during the surgery/trauma event, or increased doses of opioid exposure after the surgical or trauma event. Significant heterogeneity of study design precluded meta-analysis.ConclusionThe quality of the studies was generally of good quality; however, most studies were of US origin and used medico-administrative data. Several risk factors for POU were consistently and independently associated with increased odds of POU, primarily for surgical patients. Awareness of these risk factors may help prescribers recognise the risk of POU after surgery or trauma, when considering continuing opioids after hospitalisation. The review found gaps in the literature on trauma patients, which represents an opportunity for future research.Trial registrationPROSPERO registration: CRD42023397186.

HARNESSING ANCIENT WISDOM: PAIN MANAGEMENT IN KATIGRAHA THROUGH MARMA CHIKITSA

Background: The Ayurvedic treatment known as Marma Chikitsa stimulates Marma points to treat pain and enhance general health. The effectiveness of Marma Chikitsa in treating Katigraha, a disorder marked by stiff-ness, limited mobility, and low back discomfort, is investigated in this study. Methods: Traditional Ayurvedic texts, PubMed, and Google Scholar were searched for relevant material. Results: To reduce pain and promote healing, Marma Chikitsa concentrates on stimulating particular spots, especially Katikataruna and Kukundara Marma. These locations line up with important anatomical features related to low back discomfort. Natural anal-gesia is thought to be produced by the therapy's release of endogenous opioids and anti-inflammatory chemicals. Comparative research suggests that Marma Chikitsa provides a non-invasive, side-effect-free substitute for tradi-tional anti-inflammatory and analgesic medications, which frequently have limits on their effectiveness and pos-sible negative effects. Discussion: Marma Chikitsa's holistic method, which emphasizes the equilibrium of Pra-na (life force), works very well for treating Katigraha. This therapy treats the underlying imbalances that lead to chronic pain disorders in addition to providing instant pain relief. Marma Chikitsa may improve pain manage-ment techniques and provide patients with low back pain with a full remedy if it is included into contemporary medical methods. Conclusion: Marma Chikitsa offers a viable substitute for treating Katigraha, integrating both short-term analgesia and long-term recovery. To confirm its effectiveness and make it easier for conventional medical practices to incorporate it, further empirical research and clinical trials are required. This might lead to better patient outcomes in pain treatment.

Risk Factors for Sleep Disorders in Patients with Chronic Pain: A Meta-Analysis

Background: Chronic pain and sleep disorders frequently co-occur, exacerbating each other in a vicious cycle. This meta-analysis aimed to identify and quantify risk factors associated with sleep disorders in individuals experiencing chronic pain. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane Library databases was conducted from January 2018 to June 2024. Studies assessing sleep disorders (insomnia, obstructive sleep apnea, restless legs syndrome) in adults with chronic pain (non-cancer pain lasting &gt;3 months) were included. Data on demographics, pain characteristics, sleep measures, and potential risk factors were extracted. Meta-analyses were performed using random-effects models to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Twenty-seven studies (n = 12,453 participants) met the inclusion criteria. Chronic pain significantly increased the odds of having any sleep disorder (OR 2.83, 95% CI 2.19-3.65). Specific risk factors identified included: Female gender: OR 1.41 (95% CI 1.18-1.67); Higher pain intensity: OR 1.15 per 1-unit increase on a 0-10 scale (95% CI 1.08-1.23); Longer pain duration: OR 1.04 per year (95% CI 1.01-1.07); Presence of depression or anxiety: OR 2.32 (95% CI 1.85-2.91); Use of opioid medications: OR 1.58 (95% CI 1.23-2.04). Conclusion: Chronic pain is a substantial risk factor for sleep disorders. Gender, pain intensity, duration, comorbid mental health conditions, and opioid use emerged as modifiable risk factors. Targeted interventions addressing these factors may improve sleep outcomes in individuals with chronic pain.

S66 - The Substance Abuse Self-Stigma Scale: Reliability Among Veterans With Co-Occurring Chronic Pain and Opioid Use Disorder

S66 - The Substance Abuse Self-Stigma Scale: Reliability Among Veterans With Co-Occurring Chronic Pain and Opioid Use Disorder

Divergent histopathological and molecular patterns in chemically induced interstitial cystitis/bladder pain syndrome rat models

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a complex chronic pain disorder with an elusive etiology and nonspecific symptoms. Although numerous animal models with phenotypes similar to human disease have been established, no available regimen can consistently alleviate clinical symptoms. This dilemma led us to question whether current animal models adequately represent IC/BPS. We compared four commonly used IC/BPS rat models to determine their diverse histopathological and molecular patterns. Female rats were given single treatments with hydrochloric acid (HCL), acetic acid (AA), protamine sulfate plus lipopolysaccharide (PS + LPS), or cyclophosphamide (CYP) to induce IC/BPS. Bladder sections were stained for histopathologic evaluation, and mRNA expression profiles were examined using next-generation sequencing and gene set analyses. Mast cell counts were significantly higher in the HCL and AA groups than in the PS + LPS, CYP, and control groups, but only the AA group showed significant collagen accumulation. The models differed substantially in terms of their gene ontology and Kyoto encyclopedia of genes and genomes pathways. Our observations suggest that none of these rat models fully reflects the complexity of IC/BPS. We recommend that future studies apply and compare multiple models simultaneously to fully replicate the complicated features of IC/BPS.

Comparative Analysis of Ventilatory Responses during Stress Tests in Patients with Chronic Pain: Implications for Therapeutic Interventions.

Understanding the differences in ventilatory responses during exercise between patients with fibromyalgia and those with other chronic pain disorders is crucial for developing effective therapeutic interventions, especially in exercise to identify the better physical therapy prescription. Both populations face unique challenges that impact their ability to engage in physical activity; yet, the underlying physiological responses can vary significantly. In this context, the methodology of this study entailed conducting a comparative analysis of the ventilatory response during exercise in patients with fibromyalgia and those with other chronic pain disorders. The experimental protocol included a total of 31 participants (n = 13 diagnosed with fibromyalgia and n = 18 diagnosed with other chronic pain conditions). All participants completed a stress test, where the ventilatory parameters were measured in three stages (i.e., resting, incremental exercise, and recovery). The results revealed significant differences (p<0.05) in ventilatory responses between both groups. Patients with fibromyalgia exhibited reduced time for the aerobic threshold and a higher respiratory frequency in the anaerobic threshold compared to those with other chronic pain disorders. Furthermore, fibromyalgia patients demonstrated higher values in the ventilatory coefficient during the test and in the recovery stage. In conclusion, these differences underscore the need for tailored exercise programs that specifically address the unique ventilatory challenges faced by fibromyalgia patients to improve their physical function and overall quality of life.

Inhibition of mast cell degranulation by novel small molecule MRGPRX2 antagonists

BackgroundMas-related G-protein coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo. ObjectiveWe identified and characterized novel, potent, and selective orally active small molecule MRGPRX2 antagonists for potential treatment of mast cell-mediated disease. MethodsAntagonists were identified using multiple functional assays in cell lines overexpressing human MRGPRX2, LAD2 mast cells, human peripheral stem cell-derived mast cells, and isolated skin mast cells. Skin mast cell degranulation was evaluated in Mrgprb2em(-/-) knockout (KO) and Mrgprb2em(MRGPRX2) transgenic human MRGPRX2 knock-in (KI) mice by assessment of agonist-induced skin vascular permeability. Ex vivo skin mast cell degranulation and associated histamine release was evaluated by microdialysis of human skin tissue samples. ResultsMRGPRX2 antagonists potently inhibited agonist-induced MRGPRX2 activation and mast cell degranulation in all mast cell types tested, in an IgE-independent manner. Orally administered MRGPRX2 antagonists also inhibited agonist-induced degranulation and resulting vascular permeability in MRGPRX2 KI mice. In addition, antagonist treatment dose dependently inhibited agonist-induced degranulation in ex vivo human skin. ConclusionMRGPRX2 small molecule antagonists potently inhibited agonist-induced mast cell degranulation in vitro and in vivo as well as ex vivo in human skin, supporting potential therapeutic utility as a novel treatment for multiple human diseases involving clinically relevant mast cell activation.

Implementation, intervention, and downstream costs for implementation of a multidisciplinary complex pain clinic in the Veterans Health Administration.

To determine the budget impact of implementing multidisciplinary complex pain clinics (MCPCs) for Veterans Health Administration (VA) patients living with complex chronic pain and substance use disorder comorbidities who are on risky opioid regimens. We measured implementation costs for three MCPCs over 2 years using micro-costing methods. Intervention and downstream costs were obtained from the VA Managerial Cost Accounting System from 2 years prior to 2 years after opening of MCPCs. Staff at the three VA sites implementing MCPCs were supported by Implementation Facilitation. The intervention cohort was patients at MCPC sites who received treatment based on their history of chronic pain and risky opioid use. Intervention costs and downstream costs were estimated with a quasi-experimental study design using a propensity score-weighted difference-in-difference approach. The healthcare utilization costs of treated patients were compared with a control group having clinically similar characteristics and undergoing the standard route of care at neighboring VA medical centers. Cancer and hospice patients were excluded. Activity-based costing data acquired from MCPC sites were used to estimate implementation costs. Intervention and downstream costs were extracted from VA administrative data. Average Implementation Facilitation costs ranged from $380 to $640 per month for each site. Upon opening of three MCPCs, average intervention costs per patient were significantly higher than the control group at two intervention sites. Downstream costs were significantly higher at only one of three intervention sites. Site-level differences were due to variation in inpatient costs, with some confounding likely due to the COVID-19 pandemic. This evidence suggests that necessary start-up investments are required to initiate MCPCs, with allocations of funds needed for implementation, intervention, and downstream costs. Incorporating implementation, intervention, and downstream costs in this evaluation provides a thorough budget impact analysis, which decision-makers may use when considering whether to expand effective programming.

Evaluating the Efficacy of Two Pharmaceutical Therapies for Burning Mouth Syndrome

ABSTRACT Background: Burning mouth syndrome (BMS) is a chronic pain disorder characterized by a persistent burning sensation in the oral cavity, affecting quality of life significantly. Pharmacological therapy is commonly employed in the management of BMS, but the comparative efficacy of different pharmaceutical agents remains uncertain. Materials and Methods: This study was conducted involving 80 participants diagnosed with BMS, randomly assigned to two treatment groups: Group A received tricyclic antidepressants (TCAs), while Group B received anticonvulsants. Baseline assessments of pain intensity, oral health-related quality of life, and psychological distress were conducted using standardized measures. Treatment outcomes were evaluated at 3-month and 6-month follow-up visits. Pain intensity was assessed using a visual analog scale (VAS), while oral health-related quality of life and psychological distress were measured using validated questionnaires. Results: Both treatment groups demonstrated significant improvements in pain intensity, oral health-related quality of life, and psychological distress compared to baseline. At the 6-month follow-up, Group A (TCAs) showed a mean reduction of 70% in pain intensity from baseline, whereas Group B (anticonvulsants) exhibited a mean reduction of 65%. The difference in pain reduction between the two groups was not statistically significant (P = 0.35). Both groups also showed similar improvements in oral health-related quality of life and psychological distress measures. Conclusion: TCAs and anticonvulsants are both effective pharmaceutical therapies for managing BMS, resulting in significant improvements in pain intensity, oral health-related quality of life, and psychological distress.