Therapies For Chronic Pain Research Articles

Lessons learned from examination of Canadian medico-legal cases related to interventional therapies for chronic pain management.

Chronic pain is a common condition affecting almost one in five Canadians. One of the methods used to treat chronic pain is injection therapies. While they are considered relatively safe procedures, they do carry inherent risk that can result in adverse events. Our goal was to investigate these patient safety events to identify themes that could be used to shape practice guidelines and standards and improve patient safety. We looked at closed civil legal actions and regulatory college complaints associated with injection therapies for chronic pain in the Canadian Medical Protection Association database from 2015 to 2019. Injury was defined as that arising from, or associated with, plans or actions taken during the provision of health care, rather than an underlying disease or injury. Of the 91 cases identified, the most common reported complications were neurologic-related symptoms, injury, and infection. Fifty-eight percent (53/91) of patients experienced health care-related harm that had a negative effect on their health or quality of life. Peer experts were critical of the clinical care provided in 74% (67/91) of the cases. Provider-related (60%, 40/67), team-related (75%, 50/67), and system-related factors (21%, 14/67) were identified as contributing factors in these cases. Common examples of provider-related factors were deficiencies in clinical decision-making (48%, 19/40), failure to follow established procedures (43%, 17/40), and situational awareness (38%, 15/40). Common examples of team-related factors were deficiencies in medical record keeping (80%, 40/50) and communication breakdowns (56%, 28/50). All system-related factors were related to inadequate office procedures. We recommend that clinicians conduct appropriate physical examinations, keep up-to-date with clinical standards, and ensure their documentation reflects their assessment, the patient's condition, and the treatment rationale.

Antimicrobial therapies for chronic pain (part 2): the prevention and treatment of chronic pain.

The discovery and development of antimicrobial therapies represents one of the most significant advancements in modern medicine. Although the primary therapeutic intent of antimicrobials is to eliminate their target pathogens, several antimicrobials have been shown to provide analgesia as a secondary benefit. Antimicrobials have demonstrated analgesic effects in conditions that involve dysbiosis or potential subclinical infection (e.g ., chronic low back pain with Modic type 1 changes; chronic prostatitis/chronic pelvic pain; irritable bowel syndrome; inflammatory bowel disease; functional gastrointestinal disorders/dyspepsia; myalgic encephalomyelitis/chronic fatigue syndrome), and might even prevent the chronification of pain after acute infections that are associated with excessive systemic inflammation (e.g ., post COVID-19 condition/long Covid, rheumatic fever). Clinical studies often assess the analgesic effects of antimicrobial therapies in an observational manner, without the ability to identify causative relationships, and significant gaps in the understanding remain regarding the analgesic potential of antimicrobials. Numerous interrelated patient-specific, antimicrobial-specific, and disease-specific factors altogether contribute to the perception and experience of pain, and each of these requires further study. Given worldwide concerns regarding antimicrobial resistance, antimicrobials must continue to be used judiciously and are unlikely to be repurposed as primary analgesic medications. However, when equipoise exists among several antimicrobial treatment options, the potential analgesic benefits of certain antimicrobial agents might be a valuable aspect to consider in clinical decision-making. This article (the second in a two-part series) aims to comprehensively review the evidence on the prevention and treatment of chronic pain using antimicrobial therapies and suggest a framework for future studies on this topic.

ID: 216571 Remote Monitoring and Triage of Chronic Pain Patients With Patient-Centered Novel Digital Health Ecosystem

Introduction: Spinal Cord Stimulation (SCS) and other chronic pain therapies have typically been assessed by in-clinic pain scores. However, patient satisfaction is much more than sparsely measured pain alone. Digital technologies have made remote monitoring of comprehensive, longitudinal data now possible. Usefulness depends on both patient and care-team engagement and the ability to derive deep insights from complex data. Here we describe early versions of a custom-built novel digital health ecosystem, platform compliance and satisfaction, and potential for proactive intervention.

Sleep disorders in chronic pain and its neurochemical mechanisms: a narrative review.

Chronic pain (CP) is a prevalent problem, and more than half of patients with CP have sleep disorders. CP comorbidity with sleep disorders imposes immense suffering and seriously affects the patient's quality of life, which is a challenging issue encountered by clinicians. Although the reciprocal interactions between pain and sleep have been studied to some degree, there is still a lack of awareness and comprehensive description of CP comorbidity with sleep disorders. In this narrative review article, we summarize the current knowledge about the present estimates of the prevalence of comorbid sleep disorders in CP patients, sleep detection methods, sleep characterization in CP, and the effect of sleep disorders on CP and current therapies. We also summarize current knowledge of the neurochemical mechanisms of CP comorbidity with sleep disorders. In conclusion, insufficient attention has been paid to the role of sleep disorders in CP patients, and CP patients should be screened for sleep disorders in the clinic. Special attention should be given to a possible risk of drug-drug interaction when using two types of drugs targeting pain and sleep simultaneously. The current insight into the neurobiological mechanisms underlying CP comorbidity with sleep disorders is still rather limited.

Identification and characterisation of lipids that are positive allosteric modulators of glycine receptors.

Glycine receptors are ligand-gated ion channels that mediate fast inhibitory neurotransmission within the nervous system. They have recently emerged as targets for chronic pain therapies due to their role in nociceptive signalling. N-arachidonyl glycine is an endogenous lipid that modulates glycine receptors, however its mechanism of action remains unclear. We have identified a series of N-acyl amino acids that positively modulate glycine receptors. From this, a second series of lipids containing a phenylene-moiety within the lipid tail were synthesised. This improved their efficacy by up to 6-fold, and increased the potency of receptor activation by over 10-fold. (8-2-octylphneyl)octanoyl)glycine (OPOG) had the greatest activity - potentiating the glycine EC5 by 1500% with an EC50 of 664 nM at the α1 receptor. OPOG was also found to be analgesic and produces a dose-dependent reversal of allodynia in rodent models of neuropathic pain. The second aim of this study was to identify lipid binding sites on the glycine receptor. Molecular dynamic simulations of OPOG at the α1 receptor were conducted and indicated consistent binding within a cavity at the intracellular portion of transmembrane domains (TM) 1 and 4. This site has previously been suggested to bind neurosteroids. A cryoEM structure of OPOG bound to the zebrafish glycine receptor was also obtained and identified binding to an inter-subunit cavity between the extracellular portions of TM1(-), TM2(+) and TM3(+). This cavity has previously been shown to bind the positive allosteric modulator ivermectin. Mutagenesis of the residues identified within the two sites was indicated potentiation occurs primarily through the neurosteroid binding site involving aromatic and positively charged residues. Further studies are required to explore binding within the ivermectin cavity and its relative contribution to lipid modulation.

Protocol for a pilot and feasibility randomized-controlled trial of four weeks of oral γ-aminobutyric acid (GABA) intake and its effect on pain and sleep in middle-to-older aged adults

Approximately 1.71 billion people globally live with musculoskeletal pain conditions, including low back pain, knee pain, and neck pain Cieza et al. (2020). In the US, an estimated 20.4% of U.S. adult had chronic pain and 8.0% of U.S. adults had high-impact chronic pain, with higher prevalence associated with advancing age Dahlhamer et al. (2018). On the other hand, between 50 and 70 million US adults have a sleep disorder (American Sleep Association). Although the link between sleep and pain is widely established, the neurobiological mechanisms underlying this relationship have yet to be fully elucidated, specifically within an aged population. As currently available sleep and chronic pain therapies are only partially effective, novel treatment approaches are urgently needed. Given the potential mechanistic role of γ-aminobutyric acid (GABA) in both conditions, and the availability of GABA supplements over the counter, the present proposal will determine the feasibility and acceptability of oral GABA administration in middle-to-older aged adults with chronic pain and sleep disorders as well as characterize the potential neurobiological mechanisms involved in both conditions. Results from the present investigation using a parallel, double-blinded, placebo-controlled study will provide novel preliminary information needed for future translational pain and sleep research.

How Do Spinal Cord Stimulators Compare with Conventional Medical Therapies for Chronic Pain?

How Do Spinal Cord Stimulators Compare with Conventional Medical Therapies for Chronic Pain?

Understanding the Physiological Basis and Mechanism of Neuromodulation Therapies for Chronic Pain

Understanding the Physiological Basis and Mechanism of Neuromodulation Therapies for Chronic Pain

Modulating the activity of human nociceptors with a SCN10A promoter-specific viral vector tool

Despite the high prevalence of chronic pain as a disease in our society, there is a lack of effective treatment options for patients living with this condition. Gene therapies using recombinant AAVs are a direct method to selectively express genes of interest in target cells with the potential of, in the case of nociceptors, reducing neuronal firing in pain conditions. We designed a recombinant AAV vector expressing cargos whose expression was driven by a portion of the SCN10A (NaV1.8) promoter, which is predominantly active in nociceptors. We validated its specificity for nociceptors in mouse and human dorsal root ganglia and showed that it can drive the expression of functional proteins. Our viral vector and promoter package drove the expression of both excitatory or inhibitory DREADDs in primary human DRG cultures and in whole cell electrophysiology experiments, increased or decreased neuronal firing, respectively. Taken together, we present a novel viral tool that drives expression of cargo specifically in human nociceptors. This will allow for future specific studies of human nociceptor properties as well as pave the way for potential future gene therapies for chronic pain.

Effectiveness and Safety of Acupuncture-Related Therapies for Chronic Musculoskeletal Pain: A Protocol for Systematic Review and Network Meta-Analysis.

Chronic pain is one of the major health problems worldwide in recent years, and acupuncture-related therapies have been reported to have definite analgesic effects. However, it is still unclear which treatment is the most effective. Our systematic review and network meta-analysis protocol aims to summarize the evidence and determine the most effective method to treat the chronic musculoskeletal pain. Our literature search will be performed in five electronic databases-the Cochrane Library, EMBASE, and PubMed, AMED, CINAHL, until May 20, 2022. All randomized controlled trials of acupuncture-related therapies for chronic musculoskeletal pain will be included. The primary outcomes will be common pain-related scales, and the secondary outcomes will include quality of life and incidence of adverse events. Excel 2019 will be used for data extraction, RoB2 will be used for bias risk assessment. R 3.6.2 and WinBUGS V.1.4.3 software will be used for network data synthesis and to produce related plots. During the study, literature selection, data extraction, quality assessment and bias risk assessment will be independently completed by two reviewers, and differences will be judged by the third reviewer. Finally, the risk of bias and sources of heterogeneity in the study will be analyzed and explained in order to obtain reliable results. Our study will evaluate the effectiveness and safety of acupuncture-related therapies for the treatment of chronic musculoskeletal pain, and we will rank all methods to recommend the best appropriate treatment option. This study will provide a good foundation for complementary and alternative medicine to treat chronic musculoskeletal pain. It will be also helpful to promote the clinical practice by providing evidence-based medical evidence.

An Analysis of the Effectiveness of Integrative Therapies for Chronic Trapezius Pain

Millions suffer from chronic pain, particularly chronic back pain, but treatment-related research is limited, leading to physician overprescription of highly addictive drugs such as opioids. A common non-pharmacological treatment for chronic pain has been physical therapy, but this study examines a form of Eastern-hemisphere, mind-body techniques known as integrative therapies as a potential treatment for chronic pain in the trapezius. This study primarily analyzes acupuncture, massage therapy, and Ayurveda, three integrative therapies, to determine whether they are effective in treating chronic trapezius pain. Since integrative therapies have a large psychological component, the study also focuses on identifying whether perception of integrative therapies can influence its effectiveness and what factors can impact this perception. Through a series of interviews conducted with pain specialists, the study determines that massage therapy and Ayurveda are comparable to or more effective than physical therapy as chronic trapezius pain treatments, but the success of the therapy is dependent on the patient’s psychological perception of it. The study then conducted a survey of the general population, which revealed that while experience with integrative therapies does not appear to impact one’s perception of integrative therapy, those from an Asian/Middle Eastern background perceive integrative treatments differently and potentially perceive them as more effective. A better perception of integrative therapies leads to greater success with this treatment. These findings demonstrate that education of integrative therapies should be more widespread to counter stereotypes and misconceptions so that chronic pain treatment is, overall, more effective.

Mindfulness-Based Stress Reduction, Cognitive Behavioral Therapy, and Acupuncture in Chronic Low Back Pain: Protocol for Two Linked Randomized Controlled Trials.

BackgroundNonpharmacologic mind-body therapies have demonstrated efficacy in low back pain. However, the mechanisms underlying these therapies remain to be fully elucidated.ObjectiveIn response to these knowledge gaps, the Stanford Center for Low Back Pain—a collaborative, National Institutes of Health P01–funded, multidisciplinary research center—was established to investigate the common and distinct biobehavioral mechanisms of three mind-body therapies for chronic low back pain: cognitive behavioral therapy (CBT) that is used to treat pain, mindfulness-based stress reduction (MBSR), and electroacupuncture. Here, we describe the design and implementation of the center structure and the associated randomized controlled trials for characterizing the mechanisms of chronic low back pain treatments.MethodsThe multidisciplinary center is running two randomized controlled trials that share common resources for recruitment, enrollment, study execution, and data acquisition. We expect to recruit over 300 chronic low back pain participants across two projects and across different treatment arms within each project. The first project will examine pain-CBT compared with MBSR and a wait-list control group. The second project will examine real versus sham electroacupuncture. We will use behavioral, psychophysical, physical measure, and neuroimaging techniques to characterize the central pain modulatory and emotion regulatory systems in chronic low back pain at baseline and longitudinally. We will characterize how these interventions impact these systems, characterize the longitudinal treatment effects, and identify predictors of treatment efficacy.ResultsParticipant recruitment began on March 17, 2015, and will end in March 2023. Recruitment was halted in March 2020 due to COVID-19 and resumed in December 2021.ConclusionsThis center uses a comprehensive approach to study chronic low back pain. Findings are expected to significantly advance our understanding in (1) the baseline and longitudinal mechanisms of chronic low back pain, (2) the common and distinctive mechanisms of three mind-body therapies, and (3) predictors of treatment response, thereby informing future delivery of nonpharmacologic chronic low back pain treatments.Trial RegistrationClinicalTrials.gov NCT02503475; https://clinicaltrials.gov/ct2/show/NCT02503475International Registered Report Identifier (IRRID)PRR1-10.2196/37823

From ‘pain management’ to ‘integrated health clinic’: a quality improvement project to transition patients on chronic opioid therapy to more evidence-based therapies for chronic pain

BackgroundThe State of New York, along with the whole nation, is struggling to combat the opioid epidemic. Major authoritative bodies on chronic pain and addiction have advocated against the use...

Chronic Pain and Emotional Stroop: A Systematic Review.

Chronic pain is an unpleasant sensory and emotional experience that persists for more than 3 months and is often accompanied by symptoms such as depression, fatigue, sleep disturbances, and cognitive impairment. Emotional dysregulation may also be involved in its etiology. Emotions are known to modulate the experience of pain by influencing cognition and behavior (emotional awareness, emotional expression and experience, and verbalizations). A useful task to explore emotional processing and emotional dysregulation is the emotional Stroop task. Despite the large number of studies using this task, their objectives are diverse; it is necessary to integrate them. The main objective of the present systematic review was to determine the extent of the abnormalities in behavioral performance (including attentional biases) and/or brain alterations in patients with chronic pain during the emotional Stroop task. This systematic review was conducted in accordance with the Cochrane Collaboration guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The protocol was previously registered in the Prospective Register of Systematic Reviews (PROSPERO) international database. The selected articles were extracted from the PubMed, Scopus, and Web of Science databases. Fifteen studies were identified as eligible for systematic review. The studies reported alterations in brain regions related to pain and emotional regulation, as well as attentional bias and higher response time latencies (related to the words’ emotional load) in patients with chronic pain. The results confirm the validity of the emotional Stroop task to measure emotions and selective attention. As attentional bias towards negative information is often seen in chronic pain patients, and given the relation between selective attention and greater activation of the brain areas associated with pain and emotional processing, this type of task plays a crucial role in research on emotional and attentional processes among chronic pain patients. Further, attentional bias towards negative information has been associated with higher levels of pain. Taken together, the results suggest the need for cognitive training and an emotional approach to chronic pain therapies, especially targeting attentional biases and negative mood.

ID:15831 Targeted Peripheral Nerve Interventional Therapies for Chronic Pelvic Pain - Systematic Review Preliminary Results

Chronic pelvic pain (CPP) is defined as continuous or intermittent pain in the lower abdomen or pelvic region that is cyclical or non-cyclical in nature and lasts for six months or longer. CPP presents a major health care challenge due to the various etiologies and complex anatomy. CPP is more common in females with an estimated worldwide prevalence of 2.1 - 24%. Evidence-based guidelines for the treatment of CPP are lacking, therefore clinical interventions can be highly variable. The purpose of this review is to help define what interventional techniques have been studied for CPP and to compare their overall efficacy.

Non-pharmacological integrative therapies for chronic cancer pain

Chronic pain is one of the most detrimental symptoms exhibited by cancer patients, being an indication for opioid therapy in up to half of the patients' receiving chemotherapy and in 90% of advanced cases. Various successful non-pharmacological integrative therapy options have been explored and implemented to improve the quality of life in these patients. This review aims to highlight the mechanisms implicated; assessment tools used for cancer pain and summarize current evidence on non-pharmacological approaches in the treatment of chronic cancer pain. A review of the literature was conducted using a combination of MeSH keywords including "Chronic cancer pain," "Assessment," "Non-pharmacological management," and "Integrative therapy." Data on the approach and assessment of chronic cancer pain as well as non-pharmacological integrative options have been displayed with the help of figures and tables. Of note, non-pharmacological integrative management was divided into three subcategories; physical therapy (involving exercise, acupuncture, massage, and transcutaneous electric nerve stimulation), psychosocial therapy (e.g. mindful practices, supportive therapy), and herbal supplementation. The use of non-pharmacological integrative therapy in the management of chronic cancer pain has been grossly underestimated and must be considered before or as an adjuvant of other treatment regimens to ensure appropriate care.

The Role of the Temporoparietal Junction (TPJ) in the Patient/clinician Interaction During Evoked Pain Treatment – a Hyperscan EEG Study

The patient/clinician relationship is central in clinical therapies for chronic pain and has been linked with treatment efficacy. To assess the brain mechanisms underlying these psychosocial interactions, neurophysiological objective measures are still needed. A recent publication from our team applied functional MRI hyperscanning (synchronized neuroimaging) to demonstrate that patient/clinician brain concordance in the temporoparietal junction (TPJ) was up-regulated following a clinical interaction and this up-regulation was associated with analgesia in fibromyalgia patients. Here we propose a hyperscanning study where the patient/clinician brain response is evaluated using electroencephalography (EEG). This non-invasive neuroimaging technique allowed for an ecologically valid experimental setting with a realistic intervention as well as further characterization of TPJ dynamics in the brain-to-brain model during pain treatment. We recorded EEG simultaneously (28 dyads, 64 channels) from low-back pain patients and acupuncturists during a task with treatment and no-treatment trials in conjunction with evoked cuff pain. Using a liner-inverse approach, we reconstructed the electrical activity from 17 Regions of Interest. Statistical connectivity patterns were obtained by comparing Partial Directed Coherence estimated for treatment and no-treatment trials (α=0.05, FDR corrected) and their properties were summarized by computing the degree of each node (number of connections exchanged between brains involving a specific area). We found that TPJ was one of the dominant nodes connecting patient and clinician brain activity in Theta band. TPJ degree in the patients was significantly higher during treatment trials compared to no-treatment (p<0.01). Additionally, we found increased connectivity in clinicians' TPJ when evoked pain was being observed, but not treated. The key role of the TPJ in the patient/clinician interaction during pain treatment has now been demonstrated by both EEG and fMRI neuroimaging. Future studies will investigate how TPJ activity and concordance can predict]the quality of the patient/clinician interaction and clinical outcomes for a longitudinal treatment. Grant support from R33-AT009306.

Providing a Nursing Care Plan as a Requirement for Secondary Prevention for People Living With HTLV-1.

IntroductionThe absence of nursing care plans aimed at people living with HTLV-1 (PLHTLV) led us to develop and test a proposed nursing care plan based on the evaluation of 55 PLHTLV to outline interventions according to the clinical stage.MethodsAfter interviews with symptomatic patients, nursing diagnoses were made using the NANDA International Nursing Diagnoses (The International Nursing Knowledge Association). Subsequently, interventions were selected through the Classification of Nursing Interventions (NIC), and expected results were selected through the Classification of Nursing Outcomes (NOC).ResultsThe actual diagnoses included (ii) chronic pain, (iii) impaired urinary elimination, and (iv) sexual dysfunction; the health promotion diagnosis was (i) risk-prone health behavior; and the risk diagnoses were (i) risk of feeling powerless and (ii) risk of falls in adults. Nursing care must prevent the lack of adherence to monitoring, establish goals and promote family involvement. A safe home environment requires intervention for fall prevention. Full support in understanding pharmacological and non-pharmacological therapies for chronic pain is needed. Interventions allow patients with impaired urinary function to be reintroduced to society. For sexual dysfunction, it is necessary to discuss safe sex and behavioral changes. Regarding risk behaviors, it is necessary to guide the patient/family, adapt language to the education level of these individuals, and help them better accept the condition, among other guidelines.ConclusionThe development of a nursing care plan for PLHTLV is essential for preventing the rapid progression of disease and the improvement of the quality of life of PLHTLV and should be included in the multidisciplinary approach to the secondary level of prevention of HTLV-1.

Investigating the Long-Term Effect of an Interdisciplinary Multimodal Rehabilitation Program on Levels of Bioactive Lipids and Telomerase Activity in Blood from Patients with Chronic Pain.

Mechanism-based diagnosis and therapies for chronic pain are lacking. However, bio-psycho-social interventions such as interdisciplinary multimodal rehabilitation programs (IPRPs) have shown to be relatively effective treatments. In this context we aim to investigate the effects of IPRP on the changes in levels of bioactive lipids and telomerase activity in plasma, and if these changes are associated with changes in pain intensity and psychological distress. This exploratory study involves 18 patients with complex chronic pain participating in an IPRP. Self-reports of pain, psychological distress, physical activity, and blood samples were collected before the IPRP and at a six-month follow-up. Levels of arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamide (SEA), and telomerase activity were measured. Pain intensity was decreased, and SEA levels were increased at the six-month follow up. A significant correlation existed between changes in SEA levels and pain intensity. AEA levels, were inversely correlated with physical activity. Furthermore, 2-AG and telomerase activity was significantly correlated at the six-month follow-up. This study confirms that IPRP is relatively effective for reduction in chronic pain. Changes in SEA were correlated with changes in pain intensity, which might indicate that SEA changes reflect the pain reduction effects of IPRP.

Effectiveness of different acupuncture therapies for chronic cancer pain: A protocol for systematic review and Bayesian network meta-analysis.

Background:Pain is a common and distressing symptom experienced by cancer patients. Previous research found acupuncture was associated with significant reductions in pain intensity and opioid use. Acupuncture therapies are various, and the difference in efficacy and safety has never been assessed. This paper aims to assess and rank the effectiveness of the different acupuncture methods and provide an acupuncture treatment guideline for relieving chronic pain in cancer survivors.Methods:Four English databases (PubMed, Embase, Cochrane library, and Web of Science) and 4 Chinese databases (China National Knowledge Infrastructure, Wanfang Data, and Chinese Biomedical Literature Database) will be searched for randomized controlled trials (RCTs) published from the database inception to November 30, 2021. The primary outcomes will be patient-reported pain intensity measured by the Brief Pain Inventory, Visual Analog Scale, Verbal Rating Scale, Numerical Rating Scale, and other valid outcome measures. The Grading of Recommendations Assessment, and Development and Evaluation System will evaluate the quality of evidence. Bayesian network meta-analysis will be performed in WinBUGS V.1.4.3 to determine the comparative effectiveness of the acupuncture therapies.Results:This study will quantify the effectiveness of each acupuncture intervention for chronic cancer pain with pain scores and the use of analgesics. The adverse events of acupuncture treatment for cancer pain will also be reported.Conclusion:The conclusion of our study will help physicians and patients choose suitable acupuncture methods to manage cancer pain.