Treatment Of Chronic Pain Research Articles

Chronic Pain and Chronic Bias in Women’s Healthcare

Gender bias against women with respect to the treatment of chronic pain is evident in several ways. Recent studies reveal that women receive poorer pain management care and have less access to such care. Such disparities are further perpetuated in the type of pain management offered to females in the form of psychotherapy as compared to men who typically receive pharmacological medications. The 2023 documentary Below the Belt shows real life journeys of women battling endometriosis, illustrating how the medical system in modern America marginalizes female pain management. Women’s health issues receive less research funding, inspiring the gender biases that are prevalent across all aspects of medical healthcare and healthcare research. In addition, a lack of focus on gender and sex disparities in medical school curricula further perpetuates the problem, as medical practitioners are not educated on the differences in experience between populations. Raising issues of gender awareness and differences in care for males and females at the start of the medical journey enables the issue of gender bias in medical care to be dealt with at the root of the system. This paper aims to highlight the impact of gender bias in women’s healthcare for chronic pain within every step of the medical process.

Psychological Interventions for Chronic Pain: An Umbrella Review of Systematic Reviews and Meta-Analyses of Randomized Controlled Trials

Background: There is a continuous increase in the number of studies showing that psychological interventions help reduce chronic pain. Systematic review studies that analyze the effect are also increasing. The aim of this umbrella review was to synthesise the best available research evidence for the effectiveness of standardised psychological interventon for adults with chronic pain.Methods: Using MEDLINE (PubMed) and Cochrane CENTRAL search engines, four systematic reviews met the study criteria, including 60 randomized control trials and 7,025 patients with chronic pain.Results: Compared to waiting control and treatment as usual, psychological interventions displayed medium effect sizes for pain intensity (SMD −0.35, CI −0.42 to −0.29, 4 reviews, N=4,061), pain disability (SMD −0.44, CI −0.51 to −0.36, 3 reviews, N=2,609), and physical functioning (SMD 0.38, CI 0.29 to 0.48, 2 reviews, N=1,699). Additionally, psychological interventions exhibited a medium effect size in reducing pain intensity (SMD −0.34, CI −0.42 to −0.26, 2 reviews, N=2,508) and pain disability (SMD −0.43, CI −0.51 to −0.35, 2 reviews, N=2,563) in chronic low back pain.Conclusions: The results reaffirm that psychological interventions, along with drug or conventional treatments, can be helpful in managing chronic pain.

Inflammatory pain resolution by mouse serum-derived small extracellular vesicles

Current treatments for chronic pain have limited efficacy and significant side effects, warranting research on alternative strategies for pain management. One approach involves using small extracellular vesicles (sEVs), or exosomes, to transport beneficial biomolecular cargo to aid pain resolution. Exosomes are 30–150 nm sEVs that can be beneficial or harmful depending on their source and cargo composition. We report a comprehensive multi-modal analysis of different aspects of sEV characterization, miRNAs, and protein markers across sEV sources. To investigate the short- and long-term effects of mouse serum-derived sEVs in pain modulation, sEVs from naïve control or spared nerve injury (SNI) model male donor mice were injected intrathecally into naïve male recipient mice. These sEVs transiently increased basal mechanical thresholds, an effect mediated by opioid signaling as this outcome was blocked by naltrexone. Mass spectrometry of sEVs detected endogenous opioid peptide leu-enkephalin. sEVs from naïve female mice have higher levels of leu-enkephalin compared to male, matching the analgesic onset of leu-enkephalin in male recipient mice. In investigating the long-term effect of sEVs, we observed that a single prophylactic intrathecal injection of sEVs two weeks prior to induction of the pain model in recipient mice accelerated recovery from inflammatory pain after complete Freund’s adjuvant (CFA) injection. Our exploratory studies examining immune cell populations in spinal cord and dorsal root ganglion using ChipCytometry suggested alterations in immune cell populations 14 days post-CFA. Flow cytometry confirmed increases in CD206+ macrophages in the spinal cord in sEV-treated mice. Collectively, these studies demonstrate multiple mechanisms by which sEVs can attenuate pain.

Spinal PTP1B Regulated NMDA Receptor-mediated Nociceptive Transmission and Peripheral Inflammation-induced Pain Sensitization.

Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of several pain-related substrates in spinal cord dorsal horn and are critically involved in the modification of pain transmission. The current study demonstrated that protein tyrosine phosphatase 1B (PTP1B), a unique endoplasmic reticulum-resident member of PTP family, displayed an activity-dependent increase in its protein expression and synaptic localization in spinal dorsal horn of adult male rats. PTP1B interacted with the Src Homology 3 (SH3) domain of Synapse-Associated Protein 102 (SAP102), one of the postsynaptic scaffolding proteins that anchored PTP1B at postsynaptic sites. The SAP102-tethered PTP1B augmented the synaptic transmission mediated specifically by GluN2B subunit-containing N-methyl-D-aspartate subtype glutamate receptors. Interference with PTP1B activity or disruption of its interaction with SAP102 attenuated GluN2B-mediated nociceptive transmission and ameliorated pain sensitization induced by intraplantar injection of Complete Freund's Adjuvant. These data suggested that the activity-dependent synaptic redistribution of PTP1B served as an important mechanism regulating GluN2B receptor activity and that manipulation of PTP1B synaptic targeting might represent an effective approach for the treatment of chronic inflammatory pain.

The use of the 360 MD Huber platform in rehabilitation of lumbar radiculopathies, chronic period

Low back pain (LBP) is a common medical condition with a negative impact on quality of life and work. It also leads to financial costs for the health system by increasing the costs of medical treatment. Numerous studies have focused on the effects of exercise, with some highlighting the role of protective studies in LBP while other studies have shown no beneficial. There is moderate-certainty evidence that therapeutic exercise is beneficial in the treatment of chronic low back pain compared with other treatment modalities. Muscle strengthening and the creation of spinal mobility through specific exercise is a recognized therapeutic approach to the prevention and treatment of LBP. The main objecvtive is to evaluate the effectiveness of a physi-cal therapy program utilizing the 360 Huber platform on the quality of life for individuals with chronic lumbar radiculopathy. A randomized controlled trial was conducted with 30 participants diagnosed with chronic lumbar radiculopathy. Participants were divided into an ex-perimental group (n=20) receiving the 360 Huber platform-based rehabilitation protocol, and a control group (n=10) continuing standard care. The intervention included 15 sessions of physical therapy on the 360 Huber platform, complemented by electrotherapy and therapeutic massage. The Oswestry Disability Index (ODI) was administered pre- and post-intervention to assess changes in functional outcomes and quality of life. The experimental group demonstrat-ed a significant reduction in ODI scores, with an average decrease of 1.85 points (10.11%) from 18.30 to 16.45. The paired t-test analysis revealed a statistically significant difference (p < 0.001) and a very large effect size (1.11), indicating substantial improvements in functional outcomes. The control group showed no significant changes. The rehabilitation protocol using the 360 Huber platform, combined with electrotherapy and therapeutic massage, effectively im-proves functional outcomes and quality of life for patients with chronic lumbar radiculopathy. The study highlights the potential of integrating advanced technology with traditional physical therapy methods to enhance treatment efficacy. Future research with larger sample sizes and longer follow-up periods is recommended to confirm these findings and explore additional therapeutic modalities.

Dual Kv7.2/3-TRPV1 modulators inhibit nociceptor hyperexcitability and alleviate pain without target-related side effects.

Persistent or chronic pain is the primary reason people seek medical care, yet current therapies are either limited in efficacy or cause intolerable side effects. Diverse mechanisms contribute to the basic phenomena of nociceptor hyperexcitability that initiates and maintains pain. Two prominent players in the modulation of nociceptor hyperexcitability are the transient receptor potential vanilloid type 1 (TRPV1) ligand-gated ion channel and the voltage-gated potassium channel, Kv7.2/3, that reciprocally regulate neuronal excitability. Across many drug development programs targeting either TRPV1 or Kv7.2/3, significant evidence has been accumulated to support these as highly relevant targets; however, side effects that are poorly separated from efficacy have limited the successful clinical translation of numerous Kv7.2/3 and TRPV1 drug development programs. We report here the pharmacological profile of 3 structurally related small molecule analogues that demonstrate a novel mechanism of action (MOA) of dual modulation of Kv7.2/3 and TRPV1. Specifically, these compounds simultaneously activate Kv7.2/3 and enable unexpected specific and potent inhibition of TRPV1. This in vitro potency translated to significant analgesia in vivo in several animal models of acute and chronic pain. Importantly, this specific MOA is not associated with any previously described Kv7.2/3 or TRPV1 class-specific side effects. We suggest that the therapeutic potential of this MOA is derived from the selective and specific targeting of a subpopulation of nociceptors found in rodents and humans. This efficacy and safety profile supports the advancement of dual TRPV1-Kv7.2/3 modulating compounds into preclinical and clinical development for the treatment of chronic pain.

Cannabinoids as a Natural Alternative for the Management of Neuropathic Pain: A Systematic Review of Randomized Placebo-Controlled Trials.

Dysfunction or damage to the nervous system may develop into and result in a chronic pain condition known as neuropathic pain. Neuropathic painis defined as the structural and functional alteration of the somatosensory component of the nervous system. The treatment of neuropathic pain is a complex endeavor, which often requires specialist care and intensive drug therapy. Recently, cannabinoids have emerged as an alternative and natural option for the treatment of chronic pain, with tetrahydrocannabinol (THC) and cannabidiol (CBD) being the most extensively studied neuroactive components. The therapeutic potential of cannabis remains largely underexplored, primarily due to its social stigma and the restrictions that are in place on its cultivation. The primary aim of this systematic review was to explore the therapeutic value of cannabinoids in the management of chronic pain and thus achieve an improved quality of life for those patients. A systematic review of the literature published over the last two decades was performed usingthe following databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Turning research into practice (Trip), and Google Scholar. Studies that were completed and published between January 01, 2000 and August 31, 2024, in English language, were extracted and appraised. A combination of keywords and Boolean operators Cannabis OR Chronic Pain OR End of life OR Pain Management AND Drug therapywas employed for data extraction. The Cochrane risk-of-bias tool for randomized trials (RoB 2) was used for risk-of-bias assessment. The initial search resulted in 125282 articles; 86,781 of the articles were identified as duplicates and were removed from the primary analysis, and 38,501 abstracts were thus screened. Abstracts, case studies, reports, editorials, viewpoints, cross-sectional studies, cohort studies, case-control studies, case series, and letters to the editor/correspondence manuscripts (n =38,492) were furthermore excluded. Nine full-text articles were critically assessed and tested against the inclusion and exclusion criteria, and a further four articles were excluded with a total of five placebo-controlled randomized control studies being ultimately included in the final systematic review. Compared to placebo, cannabinoids provided significant relief from chronic pain(33% vs 15%) as measured by the visual analog scale. The transdermal application of CBD led to a more pronounced reduction in sharp pain, according to the neuropathic pain scale. Minimal to no side effects were recorded, further highlighting the potential benefits of cannabinoids.

Group dynamics and therapy outcome of multimodal pain therapies: A prospective observational trial

AbstractBackgroundFor the treatment of chronic pain, interdisciplinary treatment programs are recommended. Despite continuous adaptation and optimization of this cost‐ and time‐intensive and comprehensive form of therapy, it is not successful in some patients. As personality disorders have an important influence on social interaction and behaviour, the aim of our study was to identify the possible impact of patients with personality disorders on group dynamics and to analyse the influence of group dynamics on individual therapy outcomes.MethodsWe conducted a prospective observational study in patients with chronic pain (N = 104) who participated in a 5‐week interdisciplinary treatment program. The main outcome parameters were psychological state and pain intensity before and after the program.ResultsIn contrast to our clinical assumption, we found that neither the type nor the number of patients with personality accentuation or personality disorders had a clinically relevant influence on group dynamics and that even a negative group dynamic did not negatively influence the individual therapy outcome.DiscussionThis trial analysed the connection between group dynamics and therapy outcome of multimodal pain therapies in chronic pain patients considering the factor of personality disorders. Our data demonstrated that neither the type nor the number of patients with personality disorders had a clinically relevant influence on group dynamics and that even a negative group dynamic did not negatively influence the individual therapy outcome. Hence, clinicians should not be afraid to include patients with personality disorders in their treatment programs.Significance StatementThe study emphasizes that clinicians may include patients with personality disorders in multimodal pain treatment programs and groups, provided that the maintenance of a close therapeutic bond with the patient and within the interdisciplinary team is given.

An in-Depth Exploration of Consumer and Consumer Representative Views on Chronic Pain Management in Australia: A Key Informant Interview Study

Chronic pain affects millions of Australians. Despite guidelines recommending non-pharmacological approaches as the first line treatment, opioid medications remain among the most common treatments. This study interviewed consumers and consumer representatives (i.e., representatives of peak pain advocacy organizations in Australia) to gain first-hand perspectives on chronic pain treatment in Australia. Individual semi-structured Key Informant Interviews (KIIs) with three consumers and three representatives were undertaken. Interviews were transcribed, and thematic analysis applied. Results showed that consumers and consumer representatives identified critical treatment access barriers. Another shared theme related to overarching principles of care, with sub-themes pertaining to the need for an interdisciplinary approach and pain education. A further shared theme focused on typical medical interventions, with one shared subtheme regarding the benefits and drawbacks of pain medications. Both groups highlighted the importance of a biopsychosocial approach with consideration of mental health, particularly related to perceived stigma and comorbidities. These findings highlight that chronic pain remains both undertreated and inadequately treated in Australia. There is a critical need to use novel approaches to overcome access barriers and stigma, and to advance precision medicine to match patients to the treatment most likely to be of benefit as early as possible in their journey.

Is general practitioner involvement in the initiation of opioids for chronic non-cancer pain associated with opioid dose and concurrent drug use?

Objective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.

Rat Sympathetic Neuron Calcium Channels Are Insensitive to Gabapentin.

The gabapentenoids such as gabapentin (GP) and pregabalin are approved for the treatment of chronic pain, but their utility is limited by persistent side effects. These adverse effects result from GPs affecting many types of neurons and muscle cells, not just the pain-sensing neurons that are the intended targets. We have recently discovered a type of peripheral neuron, rat sympathetic neurons from the superior cervical ganglion (SCG), that is uniquely insensitive to GP effects. Currents were measured using whole-cell patch-clamp electrophysiology from cells in primary culture from either the SCG or the Nodose Ganglion (NDG) as a positive control for the effects of GP. We find that the calcium current density was dramatically reduced by GP pretreatment in NDG neurons, but that neurons from the SCG were resistant. Further, when GP was cytoplasmically injected into these neurons, the resistance of SCG neurons to GP treatment persisted. These data demonstrate that rat sympathetic neurons appear to be uniquely resistant to GP treatment. These results may help us to better understand the mechanism of action of, and resistance to, GP in altering calcium channel current density, which may help to develop future treatments with fewer side effects.

The impact of different music genres on pain tolerance: emphasizing the significance of individual music genre preferences

Music is a promising (adjunctive) treatment for both acute and chronic pain, reducing the need for pharmacological analgesics and their side effects. Yet, little is known about the effect of different types of music. Hence, we investigated the efficacy of five music genres (Urban, Electronic, Classical, Rock and Pop) on pain tolerance. In this parallel randomized experimental study, we conducted a cold pressor test in healthy volunteers (n = 548). The primary outcome was pain tolerance, measured in seconds. No objective (tolerance time) or subjective (pain intensity and unpleasantness) differences were found among the five genres. Multinomial logistic regression showed that overall genre preference positively influenced pain tolerance. In contrast, the music genres that participants thought would help for pain relief did not. Our study was the first to investigate pain tolerance at genre level and in the context of genre preference without self-selecting music. In conclusion, this study provides evidence that listening to a favored music genre has a significant positive influence on pain tolerance, irrespective of the kind of genre. Our results emphasize the importance of individual music (genre) preference when looking at the analgesic benefits of music. This should be considered when implementing music in the clinical setting.

Examining Psychological Distress and Learned Helplessness in Iranians Chronic Pain Patients with Differing Post-traumatic Stress Disorder Intensity: A Comparative Study

Background: Chronic pain (CP) is defined as persistent, severe pain lasting for more than three months and is often associated with psychological distress (PD) and learned helplessness (LH). Objectives: This study aims to explore the relationship between post-traumatic stress disorder (PTSD), PD, and LH in individuals with CP. Methods: The research employed a descriptive, causal-comparative methodology. The study population consisted of patients referred to pain and physiotherapy clinics in Tehran between 2022 and 2023. From a pool of 300 CP patients, 150 with high-grade PTSD severity and 150 with low-grade PTSD severity were purposively selected. Participants completed PTSD (Blevins et al., 2015), PD (Lovibond & Lovibond, 1995), and LH (Quinnells & Nelson, 1988) questionnaires. Data analysis was conducted using SPSS-24 software, with multivariate analysis of variance used for data analysis (P < 0.005). Results: Among the 300 patients, 52.6% were married, 44.0% held a bachelor’s degree, and 37.4% had musculoskeletal disorders. The findings revealed significant differences in PD and LH levels between the two groups (P < 0.001). Chronic pain patients with high-grade PTSD exhibited greater levels of depression (F = 211.09), anxiety (F = 231.06), stress (F = 374.85), and LH (F = 457.79) compared to those with low-grade PTSD (P < 0.001). Conclusions: This research highlights the significant impact of PTSD severity on PD and LH in individuals with CP. These results emphasize the need to consider psychological factors in the treatment and management of CP.

Comparison of the Effectiveness of Traditional Motorized Traction and Non-surgical Spinal Decompression Therapy Added to Conventional Physiotherapy for Treatment of Chronic Low Back Pain.

There are a limited number of studies comparing traditional motorized traction and non-surgical spinal decompression with other treatment options such as conventional motor traction in the treatment of low back pain caused by lumbar discopathy. This retrospective study aimed to compare the effectiveness of these treatments. The retrospective data of patients diagnosed with lumbar discopathy who underwent physical therapy in our clinic were reviewed. Demographic data, duration of their symptoms, physical examination findings, lumbosacral magnetic resonance imaging (MRI) reports, method and duration of treatment, and visual analog scale (VAS) and Oswestry Disability Index (ODI) results were recorded. A total of 160 patients met the inclusion criteria. Their mean age was 44.6±12.4 (range 21-65) years, 57.5% (n=92) were female, and 42.5% (n=68) were male. There were no differences between the conventional physiotherapy, motorized traction, and spinal decompression groups in terms of age, duration of symptoms, and the number of sessions (p>0.05). In all three groups, the mean scores of VAS and ODI were significantly decreased in the pre-and post-treatment comparisons (p<0.005). The rates of change in VAS and ODI were higher in the traction group and spinal decompression group compared to the conventional treatment (p<0.005). In patients with subacute and chronic lumbardiscopathies, motorized traction and spinal decompression treatments added to conventional treatment were found to be more effective than conventional treatment alone. The results of spinal decompression and conventional motorized traction treatments appear to be similar.

Exploring Veterans' Experiences Accessing Chronic Pain Treatment in the VA Community Care Network.

Chronic pain is common among Veterans, and rural Veterans commonly struggle obtaining chronic pain care due to large travel distances to the nearest Veterans Affairs (VA) medical center. In 2019, the VA established the Community Care Network (CCN) to provide Veterans access to care in community-based settings, including chronic pain management. To explore the experiences of rural Veterans receiving chronic pain treatment in the VA CCN, including their perceptions about perceived barriers, facilitators, and benefits to accessing comprehensive chronic pain management. Qualitative study using semi-structured interviews. Ten rural Veterans receiving chronic pain management in the VA CCN took part in a qualitative interview focused on their experiences accessing and utilizing the VA CCN. A descriptive qualitative approach was used. Major themes were identified through thematic content analysis. Veterans described challenges navigating the approval process, finding approved CCN providers for pain management, and they perceived that communication between the VA and community providers was not seamless. Once enrolled in the CCN, however, Veterans valued the freedom to choose providers specializing in pain management within their local communities, timely access to appointments, and opportunities to explore a wider range of pain treatment options and alternative therapies, in addition to traditional medical interventions, all in their local community. As the CCN seeks to improve collaboration between VA and community providers, recognition of Veterans' experiences could serve to drive the development of network improvements. Findings reported here suggest that Veterans preferred obtaining care in the CCN once they could navigate administrative complexity to access it. Thus, efforts to streamline VA administrative requirements for initiating CCN care would better support Veterans in meeting their needs in this context.

Who Guideline for Non-Surgical Management of Chronic Primary Low Back Pain in Adults in Primary and Community Care Settings

Low back pain is a very common condition that affects most people at some point in their lives. It represents a burden on those affected, reducing their ability to participate in activities of normal life; at the same time, dealing with it increases the economic costs of healthcare. The aim of this guideline was to contribute to WHO activities for reducing the impact of low back pain in adults and to support the WHO approach to integrated care for older people in primary care. In December 2023, the World Health Organization (WHO) published the "WHO guideline for non-surgical management of chronic primary low back pain in adults in primary and community care settings". It was developed following the process according to the WHO handbook for guideline development. The team at the WHO Collaborating Centre for Evidence-Based Medicine at the University for Continuing Education Krems (Austria) translated the summary of this guideline for its application in German-speaking countries. The guideline addresses 37 interventions for the treatment of chronic primary low back pain in primary care and provides 24 recommendations and one good practice statement. No recommendations were made regarding twelve interventions due to equivocation or lack of sufficient evidence. The recommended interventions are intended to provide a range of options to support and personalize care for adults with chronic primary low back pain.

A community health-coaching referral program following discharge from treatment for chronic low back pain – a qualitative study of the patient’s perspective

BackgroundGlobal policy and guidelines for low back pain (LBP) management promote physical activity and self-management yet adherence is poor and a decline in outcomes is common following discharge from treatment. Health coaching is effective at improving exercise adherence, self-efficacy, and social support in individuals with chronic conditions, and may be an acceptable, cost-effective way to support people in the community following discharge from treatment for LBP.AimThis qualitative study aimed to understand which aspects of a community over-the-phone health-coaching program, were liked and disliked by patients as well as their perceived outcomes of the service after being discharged from LBP treatment.MethodsA purposive sampling approach was used to recruit 12 participants with chronic LBP, from a large randomised controlled trial, who were randomly allocated to receive a health coaching program from the Get Healthy Service® in Australia. Semi-structured interviews were conducted, and a general inductive thematic analysis approach was taken.ResultsThe main themes uncovered regarding the intervention included the positive and negative aspects of the health coaching service and the relationship between the participant and health coach. Specifically, the participants spoke of the importance of the health coach, the value of goal setting, the quality of the advice received, the benefits of feeling supported, the format of the coaching service, and LBP-specific knowledge. They also reported the health coach and the coaching relationship to be the primary factors influencing the program outcomes and the qualities of the coaching relationship they valued most were connection, communication, care, and competence. The sub-themes uncovered regarding the outcomes of the intervention included positive impacts (a greater capacity to cope, increased confidence, increased motivation and increased satisfaction) and negative impacts (receiving no personal benefit).Clinical implicationsIn an environment where self-management and self-care are becoming increasingly important, understanding the patient’s experience as part of a coaching program is likely to lead to improved quality of health coaching care, more tailored service delivery and potentially more effective and cost-effective community-based care for individuals with chronic LBP in the community after being discharged from treatment.Trial RegistrationThe GBTH trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000889954) on 10/9/2020. Ethical approval was prospectively granted by the Western Sydney Local Health District Human Research and Ethics Committee (2020/ETH00115). Written informed consent was obtained from all participants. The relevant sponsor has reviewed the study protocol and consent form.

Classical, spaced, or accelerated transcranial magnetic stimulation of motor cortex for treating neuropathic pain: A 3-arm parallel non-inferiority study

BackgroundRepetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) at high frequency (HF) is an effective treatment of neuropathic pain. The classical HF-rTMS protocol (CHF-rTMS) includes a daily session for one week as an induction phase of treatment followed by more spaced sessions. Another type of protocol without an induction phase and based solely on spaced sessions of HF-rTMS (SHF-rTMS) has also been shown to produce neuropathic pain relief. However, CHF-rTMS and SHF-rTMS of M1 have never been compared regarding their analgesic potential. Another type of rTMS paradigm, called accelerated intermittent theta burst stimulation (ACC-iTBS), has recently been proposed for the treatment of depression, the other clinical condition for which HF-rTMS is proposed as an effective therapeutic strategy. ACC-iTBS combines a high number of pulses delivered in short sessions grouped into a few days of stimulation. This type of protocol has never been applied to M1 for the treatment of pain. Methods/DesignThe objective of this single-centre randomized study is to compare the efficacy of three different rTMS protocols for the treatment of chronic neuropathic pain: CHF-rTMS, SHF-rTMS, and ACC-iTBS. The CHF-rTMS will consists of 10 stimulation sessions, including 5 daily sessions of 10Hz-rTMS (3,000 pulses per session) over one week, then one session per week for 5 weeks, for a total of 30,000 pulses delivered in 10 stimulation days. The SHF-rTMS protocol will only include 4 sessions of 20Hz-rTMS (1,600 pulses per session), one every 15 days, for a total of 6,400 pulses delivered in 4 stimulation days. The ACC-iTBS protocol will comprise 5 sessions of iTBS (600 pulses per session) completed in half a day for 2 consecutive days, repeated 5 weeks later, for a total of 30,000 pulses delivered in 4 stimulation days. Thus, CHF-rTMS and ACC-iTBS protocols will share a higher total number of TMS pulses (30,000 pulses) compared to SHF-rTMS protocol (6,400 pulses), while CHF-rTMS protocol will include a higher number of stimulation days (10 days) compared to ACC-iTBS and SHF-rTMS protocols (4 days). In all protocols, the M1 target will be defined in the same way and stimulated at the same intensity using a navigated rTMS (nTMS) procedure. The evaluation will be based on clinical outcomes with various scales and questionnaires assessed every week, from two weeks before the 7-week period of therapeutic stimulation until 4 weeks after. Additionally, three sets of neurophysiological outcomes (resting-state electroencephalography (EEG), nTMS-EEG recordings, and short intracortical inhibition measurement with threshold tracking method) will be assessed the week before and after the 7-week period of therapeutic stimulation. DiscussionThis study will make it possible to compare the analgesic efficacy of the CHF-rTMS and SHF-rTMS protocols and to appraise that of the ACC-iTBS protocol for the first time. This study will also make it possible to determine the respective influence of the total number of pulses and days of stimulation delivered to M1 on the extent of pain relief. Thus, if their analgesic efficacy is not inferior to that of CHF-rTMS, SHF-rTMS and especially the new ACC-iTBS protocol could be an optimal compromise of a more easy-to-perform rTMS protocol for the treatment of patients with chronic neuropathic pain.

Efficiency of Lidocaine Intramuscular and Intraosseous Trigger Point Injections in the Treatment of Residual Chronic Pain after Degenerative Lumbar Spinal Stenosis Decompression Surgery.

Introduction: Despite the long-term use of intramuscular and intraosseous lidocaine trigger point injections (LTPI) in the treatment of patients with low back pain, there have been no studies examining their efficiency in treatment of residual pain after degenerative lumbar spinal stenosis (DLSS) decompression surgery. The purpose of our research is to examine the LTPI efficiency in the treatment of residual lumbar pain after DLSS decompression surgery and to compare the analgesic and recovery effects of intramuscular and intraosseous LTPI administered in the L4-S1 region and in the posterior superior iliac spine (PSIS) after treatment and during four months of follow-up. Materials and Methods: We observed 99 patients (F:50, M:49) aged 42 to 59 years with residual neurological disorders after DLSS decompression surgery. In all patients, the pain syndrome exceeded 6 points on the VAS and averaged 7.2 ± 0.11 points. The control group (n = 21) underwent only pharmacotherapy. In addition to pharmacotherapy, the LTPI group underwent intramuscular LTPI in L4-S1 (n = 20), intramuscular LTPI in the PSIS (n = 19), intraosseous LTPI in L5, S1 (n = 20), and intraosseous LTPI in the PSIS (n = 19). A neurological examination was carried out before treatment, 7 days after completion of treatment, and at the end of the second and fourth months of the follow-up period. Results: In the control group, intramuscular LTPI in L4-S1 subgroup, intramuscular LTPI in PSIS subgroup, intraosseous LTPI in L5, S1 subgroup, and intraosseous LTPI in PSIS subgroup, the severity of pain decreased after treatment by 27.1% (p ≤ 0.05), 41.7% (p ≤ 0.01), 50.7% (p ≤ 0.01), 69% (p ≤ 0.01), and 84.7% (p ≤ 0.01), respectively, and at the end of the second month of follow-up, by 14.3% (p > 1), 29.2% (p ≤ 0.05), 38% (p ≤ 0.01), 53.5% (p ≤ 0.01), and 72.2% (p ≤ 0.01), respectively. Reduction of neurogenic claudication, regression of sensory deficit, increase of daily step activity, and improvement of quality of life after treatment were noted in intramuscular LTPI subgroups by 19.6% (p ≤ 0.05), 36.4 (p ≤ 0.05), 40.3% (p ≤ 0.01), and 21.0% (p ≤ 0.05), respectively, and in interosseous LTPI subgroups by 48.6% (p ≤ 0.01), 67.4% (p ≤ 0.01), 68.3% (p ≤ 0.01), and 46% (p ≤ 0.01), respectively. Conclusions: LTPI is highly effective in the treatment of patients with residual pain after DLSS decompression surgery. High analgesic effect, significant regression of sensory deficits and gait disorders, and remarkable improvement of daily step activity and quality of life are noted not only after the end of LTPI treatment but also continue for at least 2 months after treatment. Intraosseous LTPI is more effective than intramuscular LTPI by 92%, and LTPI in PSIS is more effective than LTPI in L4-S1 by 28.6%.

Antinociceptive activity of transdermal nanostructured surfactant-based systems containing duloxetine hydrochloride

Duloxetine hydrochloride (DLX) is a serotonin and norepinephrine reuptake inhibitor that is effective in the treatment of chronic pain. However, the drug has several adverse reactions and extensive hepatic first-pass effect. This study aimed at developing surfactant-based formulations such as liquid crystals (LCs) and evaluating the influence of the formulations on DLX skin permeation and in vivo antinociceptive activity. Thereafter, the formulations were obtained using PEG-40 Hydrogenated Castor Oil, Tween 80, licuri oil and water. The systems selected showed isotropy, high viscosity and rheology suggestive of LCs. The systems presented ability to permeate DLX through the skin. ATR-FTIR demonstrated that formulations promoted lipid disorganization and modification of protein conformation, facilitating the drug diffusion through the stratum corneum. Moreover, the formulation loaded with DLX showed high antinociceptive activity in mice (tests of acetic acid-induced abdominal writhing, formalin and tail immersion) via the transdermal route. The antinociceptive activity was close to that of morphine (i.p.). In conclusion, the LC obtained proved to be a promising system for transdermal delivery of DLX and pain management.