Pain and Therapy最新文献

Introduction: Musculoskeletal conditions are a significant health challenge and second leading cause of disability worldwide. Diclofenac sodium topical gel 1% (DSG1%) provides effective relief of arthritis pain. While clinical studies show that DSG1% is safe and well-tolerated, long-term safety and tolerability in real-world settings are limited. This study aimed to profile users and prescribers of DSG1% and to evaluate its safety and tolerability over a screening period of 8.5 years with an average follow-up of nearly 1 year. The focus was on patients with risk factors and comorbidities, especially those taking concomitant medication in addition to topical nonsteroidal anti-inflammatory drugs (NSAIDs).

Methods: This retrospective, longitudinal cohort study used the US Department of Defense (DoD) electronic health records (EHR) database. The database included 521,593 individuals with ≥ 1 prescription for DSG1% for either indicated or non-indicated conditions with mean (standard deviation; SD) follow-up of 348.4 (562.4) days. The primary outcome measure assessed the incidence of predefined events of interest (EOIs), including gastrointestinal, hepatic, renal diseases, cardiovascular events, hypertension, skin reaction, misuse, abuse, and death (all-cause mortality).

Results: The average age of subjects was 56.7 years (SD = 18.1), with women comprising 60.4% of population. During study-period, 74.2% of subjects experienced no adverse EOIs after initiating treatment with DSG1%. Among the remaining 25.8%, average time to first EOI was 244.0 (SD = 368.6) days. Notably, the frequency of reported EOIs increased with age. Additionally, subjects with conditions such as rheumatoid arthritis, systemic lupus erythematosus, or diabetes had a higher incidence of cardiovascular EOIs.

Conclusions: The study results indicate that DSG demonstrated a favorable safety profile, particularly for patients with comorbidities and high-risk factors and when used with other medications. Despite an older population and high baseline risk factors (93%), only 26% DSG1% users experienced a predefined EOI, observed on average 244.0 (368.6) days from index date. These findings confirm the long-term tolerability of topical DSG1% for musculoskeletal disorders.

Introduction: Phase 3 clinical trials in moderate-to-severe acute pain have shown that co-crystal of tramadol-celecoxib (CTC) has improved efficacy and comparable tolerability versus immediate-release tramadol 50 mg alone, with a similar tramadol daily dose, over a 48-h treatment period. However, it is not known how first-dose tolerability compares, given that the administered dose of tramadol is higher in CTC 200 mg (88 mg) versus immediate-release tramadol 50 mg. This was explored in a post hoc analysis of a pivotal phase 3 trial.

Methods: A randomized, double-blind, factorial, active- and placebo-controlled phase 3 trial was conducted in patients with moderate-to-severe acute postoperative pain (NCT03108482) and has been previously reported. This post hoc analysis evaluated the prevalence of the four most common study drug-related, opioid-associated, treatment-emergent adverse reactions reported in phase 3 CTC clinical trials: somnolence, nausea, dizziness, and vomiting. Prevalence was evaluated in 2-h intervals, up to 6 h post first dose (just before second-dose administration) of CTC 200 mg or immediate-release tramadol 50 mg p.o. Descriptive analysis was performed.

Results: Each group comprised 183 participants for analysis. The proportions of patients reporting drug-related, treatment-emergent adverse reactions of somnolence, nausea, dizziness, and vomiting were similar between treatment groups at 2, 4, and 6 h following the first dose.

Conclusions: This post hoc analysis indicates that the higher dose of tramadol (88 mg) given in CTC 200 mg did not result in an increase in drug-related adverse reactions after first-dose administration, and had a similar tolerability profile, compared with immediate-release tramadol 50 mg alone (the lowest dose recommended for the management of moderate-to-severe acute pain). This is in line with earlier findings for the 48-h treatment period of this phase 3 trial and may be explained by CTC's differentiated physiochemical properties related to its co-crystal structure. These findings may have utility for practicing clinicians.

Trial registration: ClinicalTrials.gov identifier, NCT03108482.

Introduction: Opioid-induced constipation (OIC) is a common side effect of chronic opioid therapy that significantly impacts quality of life and healthcare costs. Naldemedine, a peripherally acting mu-opioid receptor antagonist, has shown efficacy in treating OIC. However, real-world evidence on naldemedine use in the United States is limited, particularly in older adults. We aimed to describe naldemedine use in real-world settings in the US, focusing on clinical characteristics, comorbidity profiles, co-prescribed medications, and healthcare resource utilization (HCRU), with a specific emphasis on older adults.

Methods: This retrospective study analyzed data from the 2017-2022 Merative™ MarketScan^® Commercial and Medicare Databases. We identified 2110 naldemedine users aged ≥ 30 years on chronic opioid therapy. Demographic and clinical characteristics, co-prescribed medications, and HCRU were evaluated. Subgroup analysis focused on patients aged ≥ 65 years.

Results: The study cohort (66% women, median age 56 years, 14% aged ≥ 65 years) presented a significant comorbidity burden, with 57% having hypertension, 36% diabetes, and 25% chronic pulmonary disease with a Charlson Comorbidity Index ≥ 2 in 38% of subjects. Polypharmacy (i.e., use of five or more distinct drugs, excluding naldemedine) was very common (76%, 82% in ≥ 65 years). The most frequent indications for naldemedine were chronic back pain and radiculopathy. Oxycodone, hydrocodone, and morphine were the most commonly prescribed opioids. After initiating naldemedine, 30% of patients showed a reduction in hospitalizations per patient per year, with a more pronounced effect in older adults (37%). Potential drug-drug interactions with CYP3A4 inducers or inhibitors were infrequent and did not appear to impact HCRU.

Conclusions: This real-world study demonstrates that naldemedine is predominantly used in middle-aged adults with comorbidities and polypharmacy. Naldemedine use was associated with reduced HCRU, particularly in older adults, suggesting potential benefits in managing OIC. The findings support the safety and effectiveness of naldemedine in real-world settings, including in older patients with multiple comorbidities.

Introduction: Vulvodynia is a debilitating sexual disorder with a high prevalence of 7-11%. In the study reported here, we analyzed long-term results from a prospective, non-controlled observational study to enhance our understanding of the success of therapeutic local anesthesia (TLA) and to investigate factors that predict a response or failure of therapy, with the overall aim to gain new insights into the complex medical condition of vulvodynia.

Methods: A total of 45 patients diagnosed with severe chronic vulvodynia or chronic vulvar pain (Numeric Analog Scale [NAS] ≥ 6, median 7.9, duration ≥ 6 months, median 65.2 months) and previously treated with TLA were re-evaluated 4.5-13 years after therapy. Therapy response was defined as NAS ≤ 4 for at least 6 months.

Results: Of the 45 patients originally diagnosed with vulvodynia, 38 were available for follow-up (32 of the original 36 responders, and 4 of the 9 non-responders). The average follow-up period was 7.9 years (95.2 months, range 55-156 months) after the end of therapy. All responders remained symptom-free, and two of the non-responders also became responders. Factors associated with non-response were: the number of physicians seen previously, lichen sclerosus, previous traumata, relapses of recurrent cystitis, corticoid therapy, and psychological factors, including depression, psychotropic drug intake, and psychotherapy. Body mass index (BMI) was lower in non-responders. The number of deliveries, cesarean sections, abortions, age, hormonal status, other medication intake, and gynecological surgeries had no impact on the results.

Conclusion: The long-term success of TLA supports the hypothesis that neuralgia of one or more nerves of the pelvic floor is an important component in the development of vulvodynia. This study provides evidence for the long-term effectiveness of TLA in women with vulvodynia, as well as potential obstacles to healing. Despite limitations imposed by a monocentric, non-controlled observational design, the robustness of this investigation lies in the long observation period after treatment and the substantial percentage of patients for whom TLA was successful. The long-term results emphasize the necessity of a holistic approach integrating the view of vulvodynia as a peripheral neuro-functional disorder.

Introduction: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) were the first preventive migraine treatment group to target the underlying cause of migraine. This survey evaluated real-life experiences of adults with migraine in Finland before and after using their current subcutaneous CGRP mAb treatment.

Methods: Adult users of a subcutaneous CGRP mAb for migraine prevention were recruited for an electronic cross-sectional survey by Finnish community pharmacies and Migraine Finland (a patient advocacy group) in 2023. The survey included questions regarding monthly migraine headache days, absenteeism, general disability, pain intensity, treatment patterns, and a validated Migraine-Specific Quality of Life (MSQoL) questionnaire.

Results: The survey was completed by 383 users of subcutaneous CGRP mAb medication, of whom 78 (20.4%) were receiving galcanezumab. Users of galcanezumab, the latest CGRP mAb to be reimbursed in Finland, had more previous CGRP mAb treatment switches than users of other CGRP mAbs. Following any subcutaneous CGRP mAb use, changes were observed in the number of monthly migraine headache days (0-7 experienced by 17/379 participants [4.5%] with data before, versus 302/379 [79.7%] after using treatment; ≥ 12 experienced by 279/379 [73.6%] before, versus 34/379 [9.0%] after), monthly sick leave days (from 139/376 [37.0%] to 15/376 [4.0%] with ≥ 4 monthly sick leave days), overall ability to work or study (from 180/377 [47.7%] to 287/377 [76.1%] able to work or study full time) and average intensity of migraine pain (median [lower-upper quartile] from 8.0 [7.0-9.0] before to 6.0 [4.0-8.0] after). No differences were observed between total MSQoL scores for new (0-6 months CGRP mAb use) versus persistent (≥ 6 months use) users of any CGRP mAb.

Conclusions: Patient experiences of using subcutaneous CGRP mAbs in Finland showed improvements in several migraine-related factors, supporting the potential for CGRP mAbs to improve the quality of life of adults with migraine.

This review summarizes the intraoperative anesthesia protocols for radiofrequency thermal coagulation in the treatment of trigeminal neuralgia, focusing on the advantages and disadvantages of two primary anesthesia approaches. The first approach involves the injection of local anesthetics, such as lidocaine, at the radiofrequency target, which can alleviate pain during the procedure but carries potential risks. The second approach discusses the efficacy of intravenous administration of propofol for pain control, highlighting the necessity for vigilant monitoring of vital signs during the procedure. This article aims to provide the latest evidence-based guidance for anesthesia protocol selection in clinical practice.

Neuropathic pain (NP) has a population presence of up to 10%. Both systemic agents and topical agents are recommended as first-line therapy for the treatment of NP but monotherapy provides adequate pain relief only in < 50% of the cases. This has created the need for multimodal combination therapy, a practice that is becoming more common. Combination therapy with multiple systemic agents has a risk for drug-drug interactions and adverse events (AEs), while add-on therapy with a topical agent such as lidocaine patches minimizes such risks. The focus of this review was to find if there is evidence from trials that combination therapy of the topical lidocaine patches with systemic agents will have better efficacy and/or less risk of AEs than the combination of two systemic agents. Since gabapentinoids are one of the most common systemic agents used in first-line NP therapy, the objective of this review was to summarize the safety and efficacy data and evaluate the benefit-risk ratio from three gabapentinoid combinations; gabapentinoid plus opioids, gabapentinoid plus antidepressants, and gabapentinoid plus topical lidocaine patches. Reviews of clinical trials of combinations of gabapentinoids plus other systemic agents (opioids or antidepressants) were associated with increased AEs and dropouts while improvement in analgesic efficacy was inconsistent. Clinical trials where the patients were provided topical lidocaine patches when their first treatment with a gabapentinoid was inadequate demonstrated improved analgesic efficacy with minimal additional AEs. This led to the conclusion that topical lidocaine patches-associated with minimal systemic adverse effects and proven benefits in various neuropathic pain (NP) conditions-can enhance the likelihood of achieving meaningful pain relief when used as adjuvant therapy for NP.

Introduction: Chronic low back pain (LBP) is a leading cause of healthcare expenditure and long-term disability associated with complex treatment challenges and the need for progressively invasive interventions. Percutaneous 60-day Peripheral Nerve Stimulation (PNS) is a minimally invasive neurostimulation treatment that has shown efficacy for chronic LBP, providing sustained improvements through 1 year of follow-up after treatment. The present work explores the long-term clinical outcomes of Percutaneous 60-day PNS for chronic LBP approximately 4 years after initial treatment.

Methods: Follow-up surveys were sent to participants from a prior prospective study who reported clinically meaningful reductions in pain, disability, or pain interference 12 months after Percutaneous 60-day PNS for LBP. The present long-term follow-up survey assessed current levels of LBP, disability, pain interference, and Patient Global Impression of Change (PGIC). Use of medications and other interventions for LBP treatment since completing Percutaneous 60-day PNS was also surveyed.

Results: In total, 23 participants returned completed long-term follow-up surveys. A majority of survey respondents (65%, n = 15/23) reported sustained, clinically meaningful (≥ 30%) relief of back pain compared with baseline an average of 4.7 years after PNS treatment was initiated. On average, these long-term responders reported clinically substantial (≥ 50%) reductions in pain (average 63% reduction), as well as clinically meaningful improvements in disability and quality of life. Furthermore, 70% (n = 16/23) of survey respondents avoided progression to more costly, invasive, and/or destructive LBP pain interventions (i.e., radiofrequency ablation, neurostimulation implant, or lumbar surgery).

Conclusions: Treatment with Percutaneous 60-day PNS provided clinically meaningful pain relief among a majority of surveyed participants an average of more than 4 years after the short-term treatment. These results demonstrate that Percutaneous 60-day PNS can provide durable outcomes that are often sustained for multiple (4+) years by patients with chronic axial LBP who subsequently avoid the need for more invasive treatment interventions.

Clinical trial registration: The Clinicaltrials.gov registration number for the initial study is NCT03179202.

Fibromyalgia syndrome (FMS) presents a complex and challenging disorder in both the diagnosis and treatment, with emerging evidence suggesting a role of small fibre pathology (SFP) in its pathophysiology. The significance of the role of SFP in FMS remains unclear; however, recent evidence suggests degeneration and dysfunction of the peripheral nervous system, particularly small unmyelinated fibres, which may influence pathophysiology and underlying phenotype. Both skin biopsy and corneal confocal microscopy (CCM) have consistently demonstrated that ~ 50% of people with FMS have SFP. CCM, a non-invasive measure of small nerve fibres has detected small fibre loss, correlating with neuropathic pain descriptors. Additionally, quantitative sensory testing has shown abnormalities, primarily in pain pressure/mechanical pain thresholds. This narrative review provides a comprehensive understanding of the pathophysiological dimensions of FMS with a clear focus on small nerve fibres and the peripheral nervous system, offering a roadmap for future research.

Introduction: Strategies to reduce pharmacologic use for pain are needed. Pulsed electromagnetic field (PEMF) therapy is a noninvasive, nonpharmacologic treatment for pain that modifies nitric oxide signaling to improve healing. This study examined whether PEMF decreased pain and pharmacologic use vs. standard-of-care (SOC) treatment for joint and soft tissue pain.

Methods: This prospective, randomized controlled trial enrolled 120 patients presenting with joint or soft tissue pain at five orthopedic clinic sites. The PEMF group self-administered daily therapy from a commercially available device and the SOC group received standard treatment daily as prescribed by the clinician. Patients recorded their pain level, pharmacologic usage, and adverse events daily for 14 days. After 14 days, patients in the SOC group were given the option to crossover to PEMF therapy and continue for 16 days. The study was overseen by an independent clinical research organization. It was hypothesized that PEMF would be superior to SOC for pain management.

Results: PEMF treatment provided significant analgesic benefits compared to SOC. Complete data was collected for 91 patients, 48 from the PEMF group and 43 from the SOC group. The least squares mean pain score change from baseline was - 1.8 (a 36% reduction) for the PEMF group, significantly surpassing - 0.46 (a 10% reduction) for the SOC group (p < 0.0001). Pharmacologic usage decreased from 40 to 18% for the PEMF group (a 55% reduction), while the SOC group decreased from 40 to 35% (a 12% reduction). In the crossover subgroup, patients experienced an additional 18% decrease in pain score and 63% decrease in pharmacologic use after switching from SOC to PEMF treatment.

Conclusions: PEMF was significantly more effective than SOC at managing pain and reducing pharmacologic use. PEMF therapy should be considered for noninvasive, nonpharmacologic management of joint and soft tissue pain.

Trial registration: ClinicalTrials.gov ID NCT05244187.