Treatment Of Pain Research Articles

Evaluation of outcomes of clinical phenotyping-based treatment for bladder pain syndrome/interstitial cystitis

Introduction: Bladder pain syndrome/Interstitial cystitis (BPS/IC) is clinically of diverse types because different causes contribute to the development of their symptoms. It is important to classify patients into various groups based on the possible etiopathogenesis of their condition. Treatment may be tailored to each specific group according to the possible cause. Methodology: Twenty-five patients diagnosed with BPS/IC were categorized into four different clinical phenotypes (CP) based on their history of symptoms, allergy,dysfunctional voiding, neuropathic pain, and the presence of Hunner’s ulcer. Some patients could be classified into multiple groups. The patients were given oral pentosan polysulfate, and treatment specific to their CP. Patients in CP1, CP2, and CP3 groups received, respectively hydroxyzine, clonazepam, and amitriptyline. Patients with Hunner’s lesions (HL) (CP4) underwent hydro distension and ablation of the lesion, followed by intravesical instillation of heparin and hydrocortisone. The patients were evaluated using the Apollo clinical scoring (ACS) system and their clinical scores were recorded at 1, 3, and 6 month(s). Results: Among the 25 patients, 5, 7, 4, and 9 patients were classified into CP 1 – CP4 groups respectively, and were all subjected to ACS assessment. In CP1 group (allergy group), 80% (4/5) of patients responded well to the treatment and 20% (1/5) had unsatisfactory responses. In CP2 group (dysfunctional voiding group), 71.42% (5/7) patients had good, and 28.57% (2/7) had excellent responses. In CP3 group (neuropathic pain group), 28.57% (3/4) patients had excellent, and 75% (1/4) patients had good responses. In CP4 group (HL group), 33.33% (3/9) patients had unsatisfactory, 44.44% (4/9) achieved good, and 22.22% (2/9) had excellent responses. Overall, 16% (4/25) patients had unsatisfactory, 56% (14/25) attained good, and 28% (7/25) had an excellent response at the completion of the study. Conclusion: Using clinical phenotyping-based features indicative of etiology could potentially improve treatment outcomes by targeting the specific pathological processes contributing to the patients’ symptoms.

Up-regulation of IL-1β and sPLA2-III in the medial prefrontal cortex contributes to orofacial and somatic hyperalgesia induced by malocclusion via glial-neuron crosstalk

The medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the modulation of chronic pain. Our recent study demonstrated that unilateral anterior crossbite (UAC) developed the comorbidity model of temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS), which was characterized by both orofacial and somatic hyperalgesia. In the present study, UAC rats exhibited significant changes in gene expression in the mPFC. Enrichment analysis revealed that the significantly involved pathways were cytokines-cytokine receptor interaction and immune response. The expression of group III secretory phospholipase A2 (sPLA2-III) was significantly increased in the mPFC of UAC rats. Silencing sPLA2-III expression in the mPFC blocked the orofacial and somatic hyperalgesia. Immunofluorescence showed that sPLA2-III was mainly localized in neurons. The expression of interleukin-1β (IL-1β) in the mPFC significantly increased after UAC. Injection of IL-1β antibody into the mPFC blocked orofacial and somatic hyperalgesia. IL-1β was mainly localized in microglia cells. Furthermore, injection of IL-1β antibody significantly reduced the expression of sPLA2-III. These results indicate that neuroinflammatory cascade responses induced by glial-neuron crosstalk in the mPFC may contribute to the development of TMD and FMS comorbidity, and IL-1β and sPLA2-III are identified as novel potential therapeutic targets for the treatment of chronic pain in the comorbidity of TMD and FMS.

Mast cell-derived BH4 and serotonin are critical mediators of postoperative pain.

Postoperative pain affects most patients after major surgery and can transition to chronic pain. The considerable side effects and limited efficacy of current treatments underline the need for new therapeutic options. We observed increased amounts of the metabolites BH4 and serotonin after skin injury. Mast cells were primary postoperative sources of Gch1, the rate-limiting enzyme in BH4 synthesis, itself an obligate cofactor in serotonin production by tryptophan hydroxylase (Tph1). Mice deficient in mast cells or in mast cell-specific Gch1 or Tph1 showed drastically decreased postoperative pain. We found that injury induced the nociceptive neuropeptide substance P, mast cell degranulation, and granule nerve colocalization. Substance P triggered serotonin release in mouse and human mast cells, and substance P receptor blockade substantially ameliorated pain hypersensitivity. Our findings highlight the importance of mast cells at the neuroimmune interface and substance P-driven mast cell BH4 and serotonin production as a therapeutic target for postoperative pain treatment.

Integrating Chiropractic Care and Tai Chi Training for the Treatment of Chronic Nonspecific Neck Pain in Nurses: A Single-Arm Mixed-Methods Pilot Trial.

Objectives: Chronic nonspecific neck pain (CNNP) is prevalent among health care workers, with particularly high rates among nurses. Nurses experiencing CNNP often report decreased job satisfaction, increased absenteeism, and reduced productivity. In recent years, nonpharmacologic approaches have gained attention as effective treatments for the management of CNNP, with exercise and manual therapies representing two of the most common. Early evidence shows that multimodal treatments may be more effective than unimodal strategies. The purpose of this current study was to assess the feasibility and observe the clinical outcomes of combined multimodal chiropractic care (MCC) and Tai Chi (TC) for CNNP in nurses. Methods: A single-arm mixed-methods pilot trial was conducted including 16 weeks of MCC and TC in nurses with self-reported CNNP. Feasibility outcomes were recruitment, retention, and adherence to the interventions. Clinical outcomes of interest included neck pain and related disabilities. Secondary outcomes of interest were functional, affective, and work-related performance. Qualitative interviews were also conducted. Results: Of the 59 screened, 36 met the eligibility criteria, and 21 were enrolled. The retention rate was 71.4%, and adherence rates were 85.3% for MCC and 62.5% for TC classes. Multiple pain and disability-related outcomes exhibited modest improvement from baseline to 16-week follow-up. Qualitative analysis identified six emergent themes: (1) neck pain being an inherent part of nursing, (2) nurses push through their pain, (3) MCC relieves pain and is instructive for preventing pain, (4) TC provides overall relaxation, (5) both interventions increased body awareness and improved posture, and (6) scheduling difficulties were a key obstacle for participating. Conclusions: Observed reductions in neck pain and disability suggest the potential utility of combined MCC and TC interventions for managing CNNP. Along with qualitative feedback regarding facilitators and barriers to participation, the findings support and inform a future randomized trial evaluating the combined benefits of MCC and TC for CNNP in nurses. Clinical Trial Registration #NCT06523036.

Exploring the Biomarkers and Potential Mechanisms of Botulinum Toxin Type A in the Treatment of Microglial Inflammatory Activation through P2X7 Receptors based on Transcriptome Sequencing.

This study aims to explore the potential mechanism by which Botulinum toxin type A (BoNT/ A) inhibits microglial inflammatory activation through P2X7 receptors (P2X7R). BoNT/A is a promising analgesic drug, and previous studies have established that it alleviates Neuropathic Pain (NP) by inhibiting microglial inflammatory activation. This study examined the biomarkers and potential mechanisms by which BoNT/A relieves neuropathic pain by mediating microglial P2X7R and analyzing transcriptome sequencing data from mouse BV-2 microglial cells. The P2X7R agonist Bz-ATP was used to induce microglial inflammatory activation, whilst RNAseq technology was used to explore the biomarkers and potential mechanisms through which BoNT/A suppresses microglial inflammation. RNA sequencing was performed on three BV-2 cell samples treated with a P2X7R specific activator (Bz-ATP) and three BV-2 cell samples pre-treated with BoNT/A. Only data that successfully passed quality control measures were included in subsequent analysis. Initially, Differentially Expressed Genes (DEGs) were identified from BoNT/A and control samples, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Biomarkers were then identified by constructing a Protein- Protein Interaction (PPI) network and utilizing the CytoHubba plug-in in Cytoscape software. Lastly, enrichment analysis and regulatory network analysis were performed to elucidate the potential mechanism of BoNT/A in the treatment of NP. 93 DEGs related to the "cell component size regulation" GO term and enriched in the "axon guidance" KEGG pathway were identified. Subsequently, 6 biomarkers were identified, namely PTPRF, CHDH, CKM, Ky, Sema3b, and Sema3f, which were enriched in pathways related to biosynthesis and metabolism, disease progression, signal transduction, and organelle function, including the "ribosome" and "Wnt signaling pathway." Finally, a competing endogenous RNA (ceRNAs) network was constructed from 6 mRNAs, 66 miRNAs, and 31 lncRNAs, forming a complex relationship network. Six genes (PTPRF, Sema3b, Sema3f, CHDH, CKM, and Ky) were identified as biomarkers of microglial inflammatory activation following BoNT/A treatment. This finding may provide a valuable reference for the relief and treatment of neuropathic pain.

Red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1β

Our previous study has verified that activation of group Ⅰ metabotropic glutamate receptors (mGluRⅠ) in the red nucleus (RN) facilitate the development of neuropathological pain. Here, we further discussed the functions and possible molecular mechanisms of red nucleus mGluR Ⅱ (mGluR2 and mGluR3) in the development of neuropathological pain induced by spared nerve injury (SNI). Our results showed that mGluR2 and mGluR3 both were constitutively expressed in the RN of normal rats. At 2 weeks post-SNI, the protein expression of mGluR2 rather than mGluR3 was significantly reduced in the RN contralateral to the nerve lesion. Injection of mGluR2/3 agonist LY379268 into the RN contralateral to the nerve injury at 2 weeks post-SNI significantly attenuated SNI-induced neuropathological pain, this effect was reversed by mGluR2/3 antagonist EGLU instead of selective mGluR3 antagonist β-NAAG. Intrarubral injection of LY379268 did not alter the PWT of contralateral hindpaw in normal rats, while intrarubral injection of EGLU rather than β-NAAG provoked a significant mechanical allodynia. Further studies indicated that the expressions of nociceptive factors TNF-α and IL-1β in the RN were enhanced at 2 weeks post-SNI. Intrarubral injection of LY379268 at 2 weeks post-SNI significantly suppressed the overexpressions of TNF-α and IL-1β, these effects were reversed by EGLU instead of β-NAAG. Intrarubral injection of LY379268 did not influence the protein expressions of TNF-α and IL-1β in normal rats, while intrarubral injection of EGLU rather than β-NAAG significantly boosted the expressions of TNF-α and IL-1β. These findings suggest that red nucleus mGluR2 but not mGluR3 mediates inhibitory effect in the development of SNI-induced neuropathological pain by suppressing the expressions of TNF-α and IL-1β. mGluR Ⅱ may be potential targets for drug development and clinical treatment of neuropathological pain.

The effectiveness of a dynamic seat cushion in preventing neck and low-back pain among high-risk office workers: a 6-month cluster-randomized controlled trial.

This study evaluated the effectiveness of the promotion of postural shift intervention using a dynamic seat cushion on the 6-month incidence of neck and low-back pain among high-risk office workers. In a cluster-randomized controlled trial (RCT), 133 office workers were randomly assigned, at cluster level, to intervention (N=67) and control (N=66) groups. The intervention group received a dynamic seat cushion to encourage postural shifts during sitting, while the control group received a placebo seat pad. Primary outcomes were 6-month incidence of neck and low-back pain. Secondary outcomes included sitting discomfort, pain intensity, disability, and trunk muscle performance. Analyses utilized Cox proportional hazard models. During the 6-month period, 15% of participants in the intervention group developed neck pain and 10% developed low-back pain. For the control group, this was 65% and 59%, respectively. Hazard rate (HR) ratios, after adjusting for biopsychosocial factors, indicated a protective effect of the intervention for neck pain [HRadj 0.19, 95% confidence interval (CI) 0.09-0.39, P<0.001] and low-back pain (HRadj 0.16, 95% CI 0.07-0.35, P<0.001). The intervention group demonstrated a significant reduction in sitting discomfort and improvement in trunk muscle performance compared to the control group (P<0.05). However, the intervention did not reduce pain and disability in individuals experiencing pain compared to the control group. The dynamic seat cushion effectively reduced the incidence of neck and low-back pain by promoting postural shifts. These findings suggest that the key factor in reducing the risk of developing neck and low-back pain is the facilitation of postural shifts during sitting, which can potentially be achieved with other dynamic interventions designed to reduce prolonged and static sitting among office workers.

Longitudinal qualitative perspectives of adolescents in an intensive interdisciplinary pain program

ObjectivesChronic pain in children and adolescents is often associated with functional, physical, and psychosocial challenges. Intensive interdisciplinary pain treatment (IIPT) programs are effective at helping these youth regain functioning, but little is known about their perspectives prior to and during IIPT participation. This study sought to better understand how children and adolescents experience the process from evaluation to completion of the IIPT program.MethodsIndividual interviews (n = 7) were conducted at three time-points; (1) prior to initial evaluation in a pain clinic, (2) after pain clinic evaluation while considering IIPT, and (3) after completion of an IIPT program.ResultsParticipants ranged in age from 13–17 years. Across these time points, participants demonstrated changes in thoughts and perspectives. While Time 1 was associated with ambivalence, skepticism, and some hope, Time 2 was characterized by processing information about the program and resolution of some of their ambivalence. At Time 3, participants described their experience as “challenging” and “intense” and reported recognition that they had benefited from the program. Participants also wished to pass along lessons learned to future potential patients.DiscussionThis study provides information to help clinicians better approach adolescents with chronic pain who may be considering IIPT.

A Randomized Trial Evaluating Acceptance and Commitment Therapy and Smart Phone Care Management Application to Augment Buprenorphine Therapy for Opioid Use and Chronic Pain.

There is high comorbidity of opioid use disorder (OUD) and chronic pain (CP), which is often addressed by prescribing buprenorphine (BUP). While BUP is effective in preventing overdose, it does not address the psychological aspects of OUD and CP comorbidity and treatment retention rates are as low as 50%. The Virtual Opioid use disorder Integrated Chronic Pain Treatment (VOICE) study (NCT05039554) is a novel effectiveness-implementation trial to test a 12-week virtual group Acceptance and Commitment Therapy (ACT) protocol and a care management smartphone application (app; Valera Health) on pain and opioid use in patients with OUD and CP receiving BUP. Using a 2 × 2 factorial design, participants (expected N = 280) are randomized into: ACT, Valera app, ACT + Valera, or Treatment as Usual arm. This study is taking place in the Bronx, NY, a racially/ethnically diverse community that faces numerous socioeconomic stressors and is one of the nation's epicenters of the opioid epidemic. We created a culturally responsive ACT group protocol, and Valera psychoeducational material. Outcome measures include NIH HEAL Common Data Elements and ACT and Valera-specific measures. We are conducting a novel 2 × 2 trial investigating augmenting BUP treatment with ACT and Valera, with the goal that improved mental health and access to care will result in decreased and opioid use and pain interference.

Sensors and Devices Guided by Artificial Intelligence for Personalized Pain Medicine.

Personalized pain medicine aims to tailor pain treatment strategies for the specific needs and characteristics of an individual patient, holding the potential for improving treatment outcomes, reducing side effects, and enhancing patient satisfaction. Despite existing pain markers and treatments, challenges remain in understanding, detecting, and treating complex pain conditions. Here, we review recent engineering efforts in developing various sensors and devices for addressing challenges in the personalized treatment of pain. We summarize the basics of pain pathology and introduce various sensors and devices for pain monitoring, assessment, and relief. We also discuss advancements taking advantage of rapidly developing medical artificial intelligence (AI), such as AI-based analgesia devices, wearable sensors, and healthcare systems. We believe that these innovative technologies may lead to more precise and responsive personalized medicine, greatly improved patient quality of life, increased efficiency of medical systems, and reducing the incidence of addiction and substance use disorders.

Prescribed medications for alleviating suffering symptoms in patients receiving palliative care at a tertiary care hospital.

Recognizing and appropriately treating symptoms of suffering in patients receiving palliative care is a means to enhance the quality of life for both the patient and their family. The objective of this study was to determine the proportion of pharmacological treatments for symptoms of suffering and prescribing patterns in hospitalized patients receiving palliative care at a tertiary care government general hospital. This retrospective study was conducted at the Prachuapkhirikhan Hospital, Thailand. All patients over 18 years old who were admitted to the hospital and received palliative care were included. Data were collected from medical charts and analyzed using descriptive statistics. During the 3-year period of study, 296 admissions were included. Cancer, cardiovascular disease, and infectious disease were the top three primary diseases for which patients received palliative care. Dyspnea was the most reported symptom of suffering (81.08%), followed by fatigue, constipation, and pain (41.89%, 35.14%, and 25.34%, respectively). All cases experienced fatigue, depression, insomnia, and anxiety received pharmacological treatment. Dyspnea, pain, nausea/vomiting, delirium, and malignant bowel obstruction were treated in at least 80% of the cases experiencing suffering. Constipation, diarrhea, and anorexia/ cachexia were treated in approximately 66.35%, 78.57%, and 67.86% of the cases, respectively. Strong opioids were the most commonly used medication for the treatment of dyspnea or pain. Our study revealed that suffering symptoms were routinely identified in hospitalized palliative care patients. Pharmacological treatments were prescribed to manage most of these symptoms. However, there is a need to improve the quality of assessing suffering symptoms severity to enhance their effectiveness.

Sex differences in comorbid pain and opioid use disorder: A scoping review.

Opioid use disorder (OUD) and chronic pain are commonly co-occurring disorders which can exacerbate each other. Sex/gender differences have been shown in aspects of the clinical course and biological underpinnings of both OUD and chronic pain. The purpose of this scoping review is to summarize literature which has addressed sex/gender differences in relation to the confluence of OUD and chronic pain. This review focused on peer-reviewed journal articles with human subjects and addressing (a) opioid misuse, chronic opioid use or opioid use disorder (OUD), (b) chronic or persistent pain and (c) sex/gender differences in relation to OUD and/or chronic pain. Of the 146 papers identified by the search strategy, 30 met the criteria for inclusion. Charting focused on a priori themes of chronic pain, opioid misuse/OUD and sex/gender in sample, predictor and outcome variables, and key study findings. The majority of research identified was cross-sectional in nature, and sex/gender differences and treatment effects were largely included as post-hoc analyses. Together, the results of this early work align with higher prevalence for OUD in men/males and chronic pain in women/females, while adding critical information with respect to potential sex/gender differences in the development and treatment of their co-occurrence across a range of biological and psychosocial factors. Findings underline the importance of considering sex and gender in the intersection of the development and treatment of OUD and chronic pain.

Exosomal GDNF from Bone Marrow Mesenchymal Stem Cells Moderates Neuropathic Pain in a Rat Model of Chronic Constriction Injury.

Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF.

Specific back pain - effective diagnosis and treatment from the radiologist's point of view.

The diagnosis and treatment of specific back pain is important in radiology. Due to the high number of patients suffering from back pain, it is important to provide excellent diagnostic and therapeutic support.Based on a recent literature search and considering the relevant guidelines as well as expert opinions, the aspects of specific back pain important for radiologists in terms of pathogenesis, diagnosis, and treatment are presented.Clinical examination in combination with the medical history provides a valid suspected diagnosis. This should subsequently be verified radiologically. MRI is the most effective cross-sectional diagnostic method for investigating specific back pain. A conventional X-ray on two planes in a standing position can be a useful addition if postural causes are suspected. If the clinical symptoms match the morphological findings, radiological treatment can be carried out for nerve root involvement as well as for inflammatory changes of the facet joints. The improvement in symptoms after radiological therapy is considered good overall; at least a short-term improvement in symptoms can generally be achieved, but no reliable data is available regarding the long-term outcome. Using preparations containing triamcinolone, low dosages should be selected in accordance with the guidelines. Embedding in a multimodal pain therapy treatment concept should be considered.Radiology provides essential diagnostic findings regarding specific back pain. Interventional pain therapy is an effective and safe method of treating proven specific back pain. · First examine clinically, then confirm the suspected diagnosis radiologically.. · MRI is usually the method of choice.. · Interventional pain therapy should show success after a maximum of 2 interventions.. · The anti-inflammatory drug dose should be kept as low as possible.. · The individual course determines the number of interventions.. · Stueckle CA, Haage P. Specific back pain - effective diagnosis and treatment from the radiologist's point of view. Fortschr Röntgenstr 2024; DOI 10.1055/a-2371-1752.

Identification of Cytisine Derivatives as Agonists of the Human Delta Opioid Receptor by Supercomputer-Based Virtual Drug Screening and Transcriptomics.

Delta opioid receptors (DORs) are rising as therapeutic targets, not only for the treatment of pain but also other neurological disorders (e.g., Parkinson's disease). The advantage of DOR agonists compared to μ-opioid receptor agonists is that they have fewer side effects and a lower potential to induce tolerance. However, although multiple candidates have been tested in the past few decades, none have been approved for clinical use. The current study focused on searching for new DOR agonists by screening a chemical library containing 40,000 natural and natural-derived products. The functional activity of the top molecules was evaluated in vitro through the cyclic adenosine monophosphate accumulation assay. Compound 3 showed promising results, and its activity was further investigated through transcriptomic methods. Compound 3 inhibited the expression of TNF-α, prevented NF-κB translocation to the nucleus, and activated the G-protein-mediated ERK1/2 pathway. Additionally, compound 3 is structurally different from known DOR agonists, making it a valuable candidate for further investigation for its anti-inflammatory and analgesic potential.

Evaluation of a Polyherbal Spray as Supportive Therapy for Wound and Arthritis Pain in Cows

Background: This study evaluated the effectiveness of a polyherbal spray (PHS) as a supportive treatment for pain and inflammation in dairy cows with wounds and arthritis. Fifteen cows experiencing pain and inflammation were treated with PHS for 14 days or until recovery. Researchers monitored pain, swelling, activity level, recovery time and product performance. Methods: Pain and swelling were reduced as early as day 2 of PHS application, corresponding improving the activity level. The average recovery time was 3.4 days and the owners rated the product performance highly. Result: These findings suggest that PHS could be a valuable supportive therapy for managing pain and inflammation in dairy cows with wounds or arthritis

Real-world evidence evaluation on consumer experience and prescription journey of diclofenac gel in Sweden.

The aim of this study was to understand profiles of topical Voltaren gel diclofenac (VGD) 2.32 and 1.16% consumers through analyzing prescription patterns and to characterize treatment satisfaction, functional impairment, and pain relief after over-the-counter (OTC) VGD use in Sweden under real-world conditions. This observational, real-world study conducted in Sweden had retrospective and prospective segments. The retrospective secondary data segment utilized 12-month diclofenac gel prescription data from the Swedish eHealth Agency (E-hälsomyndigheten). The prospective segment included electronic surveys completed at baseline and weeks 4 and 12 by adult consumers who purchased OTC VGD to treat their pain. Secondary data analyses (n = 12,145) showed that 56.7% of patients receiving diclofenac gel were females ≥70 years old. Most patients did not switch pain treatments; the mean time between diclofenac gel refills was about 2.5 months. From the surveys (n = 264), VGD provided pain relief, indicated by improvement in 11-point pain numeric rating scale scores. Average pain severity at baseline was 5.8 - improving by a mean of 1.3 and 1.9 points at weeks 4 and 12, respectively. The majority of consumers reported improvement in daily functioning (i.e., health-related quality of life [HRQoL]), and most were at least somewhat satisfied with VGD treatment results. This real-world study provides important insights into the prescription patterns of diclofenac gel and the consumer experience with OTC VGD in Sweden. Patients rarely switched to other topical nonsteroidal anti-inflammatory drugs, and VGD consumers reported pain relief and improved HRQoL compared to baseline - resulting in treatment satisfaction.

A Pilot Interprofessional Education Curriculum for Optimizing Mental Health in Chronic Pain Treatment and Understanding Interprofessional Practice.

With the urgent need for clinicians capable of responding to the opioid crisis, an interprofessional education (IPE) pilot curriculum was launched to assess trainee self-efficacy in managing chronic pain and mental health conditions, and attitudes toward interprofessional practice among resident physicians, family nurse practitioners (FNP), and physician assistant (PA) students. This study involved the implementation of a pilot curriculum consisting of five interactive IPE sessions. All invited trainees across two academic institutions were asked to complete the assessments. Self-efficacy in managing chronic pain and mental health was measured at baseline and following IPE training using a researcher-developed tool, while attitudes toward interprofessional practice were measured with the Attitudes Toward Health Care Teams scale. Resident physicians were compared to FNP/PA students to examine differences between groups and within groups over time. The final analysis involved 25 trainees who attended at least one IPE training session and completed pre-session and post-session surveys. The total pre-session survey and post-session survey response rate was 37.5% (n=36). Self-efficacy in chronic pain management improved among the resident physician (mean=3.85 ±0.40) and FNP/PA groups (mean=3.84±0.46) (p=0.05 and p=0.001), respectively. Self-efficacy in mental health management was not significantly improved among resident physicians (mean=3.41±0.49, p=0.48), but improved among FNP/PA students (mean=3.46±0.31, p<0.001). There was no difference in attitudes toward interprofessional practice. While IPE training did not result in attitudinal changes toward interprofessional practice, it shows potential for improving self-efficacy in managing chronic pain and mental health, particularly among FNP/PA trainees. This study was limited by a small sample size of trainees included in the finalanalysis.

A Functional Restoration Program for Active Duty Service Members With Chronic Pain: Examining the Impact of Co-occurring PTSD on Treatment Response.

Standard medical intervention for chronic pain may be less effective in the presence of co-occurring PTSD. Functional restoration programs (FRPs), which combine psychological interventions and progressive exercise rehabilitation, represent an alternative to standard medical intervention for chronic pain. The objective of the current study is to evaluate a FRP serving Active Duty Service Members with chronic pain and to examine whether co-occurring PTSD symptoms are associated with differential treatment response. This is a retrospective observational study of data previously collected at Naval Medical Center San Diego approved by the Naval Medical Center San Diego Institutional Review Board. The study included 81 Active Duty Service Members, primarily Sailors and Marines, who completed a FRP, and examined pre- to post-treatment changes in Pain Impact Score-a composite measure of pain intensity, pain interference, and physical functioning-as well as measures of mental health and pain cognitions. Co-occurring PTSD symptoms were examined as a potential moderator of treatment response. Twenty-three patients (28.4%) screened positive for PTSD during baseline assessments. Repeated measures analysis of variance showed statistically significant improvement in Pain Impact Score for the full sample (P <.001). Although no significant interactions with probable PTSD were demonstrated for measures of pain intensity and physical functioning (both Ps >.05), patients screening positive for PTSD demonstrated a lesser decrease in pain interference compared to patients screening negative for PTSD (P <.01). Improvements in measures of mental health and pain cognitions were also statistically significant for the full sample (all P values <.05) and did not differ as a function of PTSD symptoms (all P values >.05). This FRP primarily serving Sailors and Marines contributed to broad overall improvements in the domains of pain and functioning as well as mental health and pain cognitions. Co-occurring PTSD symptoms were not associated with poorer treatment response on most measured outcomes.

Optimization of a Lethal, Combat-Relevant Model of Sterile Inflammation in Mice for Drug Candidate Screening.

Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue-bone matrix (TBX). The TBX at 12.5%-20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose-response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.