Pain and Therapy最新文献

Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain disorders and exert pharmacological effects by inhibiting cyclooxygenase (COX). Although previous studies have evaluated the COX inhibitory activity and selectivity of NSAIDs, none has compared COX inhibitory concentrations with the plasma concentrations of clinical doses or investigated the efficacy and adverse effects of different dosage forms. Therefore, in this study we evaluated the COX inhibitory activities and inhibition rates of clinical doses of the various NSAID formulations, especially diclofenac sodium.

Methods: Human blood and the drug (diclofenac sodium, celecoxib, ibuprofen, flurbiprofen, or etodolac) were mixed and incubated, and the supernatant was collected and quantified the COX inhibitory activity of each drug by ELISA. Logistic regression analyses were used to calculate the inhibition rates at maximum plasma drug concentration (C_max) of clinical doses of marketed formulations. For diclofenac sodium, we also calculated the concentrations at which COX inhibition rates were 50% and 80% (IC₅₀ and IC₈₀).

Results: COX-2 inhibition rate at C_max of clinical doses exceeded 50% except celecoxib 100 mg. For diclofenac sodium, the C_max at the clinical doses of the oral and suppository formulations showed almost complete inhibition of COX-2 and an inhibition rate exceeding IC₈₀ for COX-1. The C_max at repeated doses of the transdermal formulation showed an inhibition rate above IC₈₀ for COX-2 but below IC₈₀ for COX-1.

Discussion: This result explains why gastrointestinal disorders frequently occur with oral and suppository formulations of diclofenac sodium despite its relatively high COX-2 selectivity. Although the plasma drug concentration of the transdermal formulation is lower than oral and suppository formulations, it has an inhibition rate above IC₅₀ for COX-2, which is required for analgesic efficacy, and has a lower COX-1 inhibition rate than these formulations.

Conclusion: The findings explain why the transdermal formulation exerts an analgesic effect despite having a lower C_max than other diclofenac sodium formulations.

Introduction: Migraine is a debilitating neurological disorder characterized by recurrent throbbing, moderate-to-severe headaches that disrupt daily chores, leisure, and social activities of patients, impacting their overall quality of life (QoL). Despite the high disease burden, there is a scarcity of data on migraines within the Middle East (ME) region. Thus, a systematic literature review (SLR) was conducted to examine epidemiological data, treatment patterns, QoL, and unmet needs regarding migraines in the ME region.

Methods: Electronic searches were carried out using the MEDLINE® and Embase® databases via the OvidSP® platform for articles published prior to April 2024. The inclusion and exclusion criteria for the selection of studies were based on the Patients, Intervention, Comparator, Outcomes, and Study design framework, which identified 42 studies.

Results: The prevalence of migraines reported from the region ranged between 2.6 and 32%, and the average age of patients with migraines reported in these studies ranged from 27 to 37.5 years. The data indicated a gender disparity in migraine prevalence, with women exhibiting a 2- to 2.5-fold higher prevalence. Common comorbidities reported were depression, anxiety, and irritable bowel disease. Migraines significantly impact patients' physical and emotional well-being, leading to disabilities and loss of productivity. The most common triggers of migraines were sleep disorders, dietary habits, and stress. The current treatment landscape for acute migraines encompasses anti-inflammatory agents, analgesics, triptans, ditans, calcitonin-gene-related peptides, and antiemetics. However, migraines in the region are often underestimated, underreported, and undertreated. Several unmet needs persist in the region, including delayed referral along with delayed diagnosis, misdiagnosis, poor treatment adherence, limited accessibility to treatments, and a lack of awareness among health care providers and patients.

Conclusions: The SLR highlights knowledge gaps in clinical aspects and the treatment of migraines and enables clinicians to make informed decisions to ensure optimal patient outcomes in diverse clinical settings.

Introduction: This study evaluates the financial impact on healthcare payers when chronic pain patients initiate peripheral nerve stimulation (PNS) with a 60-day percutaneous PNS (60-Day PNS) treatment versus a conventional brief PNS trial (PNS-BT) with possible follow-on of a permanently implanted PNS system (PNS-PI).

Methods: Centers for Medicare & Medicaid Services (CMS) fee-for-service (FFS) data were analyzed to identify patients with at least 12 months of follow-up (median 26.4 months) who initiated PNS treatment with: (1) 60-Day PNS or (2) PNS-BT. An economic decision tree model assessed the cost to payers in each cohort. Clinical response to 60-Day PNS was estimated by retrospectively reviewing anonymized outcomes from a national real-world database, focusing on patients ≥ 65 years of age who were implanted with a 60-day percutaneous PNS system. For the economic model, a Monte Carlo simulation with 10,000 iterations was used to generate 95% confidence intervals, considering variability in treatment outcome probability and costs.

Results: Based on CMS data, among 60-Day PNS patients, 18% (229/1265) proceeded to a permanently implanted PNS system with a 4% explant rate (10/229). Among PNS-BT patients, 41% (1140/2811) received a permanent implant with a 7% rate of explant (77/1140). Estimated PNS-related weighted average costs for the 60-Day PNS cohort [US$17,344; 95% confidence interval (CI): $16,168-$18,527] were lower than the PNS-BT cohort ($24,392; 95% CI $22,865-$25,941) when considering the percent of patients who advanced to a permanently implanted PNS system. The total cost per successful outcome also favored 60-Day PNS ($25,228 per success for the 60-Day PNS cohort vs. $64,502 per success for the PNS-BT cohort) as a first-line approach in PNS treatment.

Conclusions: The findings suggest that, when PNS for chronic pain is warranted, initiating PNS with a 60-day treatment is more cost-effective than utilizing a brief conventional trial.

Introduction: Migraine is a prevalent neurological disorder causing significant disability worldwide. Despite extensive research on specific populations, comprehensive analyses of global trends are remains limited.

Methods: We extracted incidence, prevalence, and disability-adjusted life years (DALYs) data for migraine from the Global Burden of Disease 2021 database. Trends were analyzed across regions, age groups, sexes, and sociodemographic index (SDI) using estimated annual percentage changes (EAPC). Predictive models (ARIMA) were used to forecast trends to 2050.

Results: From 1990 to 2021, the global burden of migraine significantly increased: prevalence increased by 58.15%, from 732.56 million to 1.16 billion cases, and incidence increased by 42.06%. The DALYs also increased by 58.27%. There were differences between the sexes: female individuals had higher absolute rates of migraine incidence and prevalence, but male individuals exhibited a four- to five-fold more rapid increase than female individuals in these parameters. Adolescents (< 20 years old) have the fastest growth in prevalence and DALYs. Regionally, high SDI regions having the highest age-standardized rate (ASR) and low SDI regions having the lowest ASR in DALYs. East Asia and Latin America exhibited the most significant increases in migraine burden, whereas Southeast Asia exhibited the most pronounced decrease. Predictive analysis suggests prevalence will continue to rise until 2050, particularly among male individuals and adolescents.

Conclusions: The global burden of migraine has significantly escalated from 1990 to 2021, with female individuals bearing a greater burden but male individuals showing a faster growth rate. Adolescents also face a rapidly rising prevalence. Disparities across SDI regions, countries, age groups, and sexes emphasize the need for targeted public health strategies. Focused interventions are required to mitigate the growing impact of migraines on global health, particularly among male individuals and adolescents.

Introduction: The cost benefit of intercostal nerve cryoablation during surgical lobectomy for postoperative pain management is unknown. The current study compared hospital economics, resource use, and clinical outcomes during the index stay and accompanying short-term follow-up. Patients who underwent lobectomy with standard of care treatment for postsurgical pain management and cryoablation were compared to those with standard of care treatment only. We hypothesized that cryoablation would reduce narcotic use and index hospital and short-term costs.

Methods: A retrospective, propensity matched cohort of surgical patients treated between 2016 and 2022 from a US National All-Payer Database were used. Cost and outcome comparisons were made between groups using chi-square and t tests.

Results: From a cohort of 23,138 patients, 266 pairs with a mean age of 69 years were included. Matching variables included age, gender, lobe resected, and prior opioid use. Both groups had significant comorbidity history and prior opioid use; 66% (n = 175 both groups) underwent open lobectomy and 53% (n = 142 vs. 143) had the upper lobe resected. Cryoablation intervention was associated with 1.3 days reduced hospital stay (8.8 vs. 10.1 days, p = 0.31) and no difference in perioperative safety. After 90 days, postsurgery cryoablation patients had lower opioid prescription refills (27.3 vs. 36.9 morphine milligram equivalents, p = 0.03). Cryoablation patient costs trended less than non-cryoablation patients during index ($38,753 vs. $43,974, p = 0.10) and lower through 6 months (total costs, $65,703 vs. $74,304, p = 0.10). There was no difference in postsurgery resource use, but a smaller proportion of cryoablation patients had outpatient hospital visits (83.1%, N = 221 vs. 92.9%, n = 247, p < 0.01).

Conclusion: Cryoablation during lobectomy is safe and does not add incremental hospital costs. Clinical meaningful reductions in length of stay and postsurgery opioid use were observed with cryoablation intervention. The addition of cryoablation during surgery to reduce postoperative pain appears to be a cost-effective therapy.

Introduction: Pain is one of the most frequently reported symptoms in hemodialyzed (HD) patients, with prevalence rates between 33% and 82%. Risk factors for chronic pain in HD patients are older age, long-lasting dialysis history, several concomitant diseases, malnutrition, and others. However, chronic pain assessment in HD patients is rarely performed by specialists in pain medicine, with relevant consequences in terms of diagnostic and treatment accuracy. Furthermore, no study has used the recently introduced International Association for the Study of Pain (IASP) pathophysiological classification.

Methods: In this observational, cross-sectional study in a tertiary HD center in Northern Italy, we analyzed data regarding HD patients, evaluated for 5 months in 2021 by specialists in pain medicine and aimed to identify and characterize chronic pain according to the IASP definition and the last 2019 classification of chronic pain for ICD-11. Pain severity was evaluated by the pain severity score of the brief pain inventory tool.

Results: Among 213 patients, 65 (31%) suffered from chronic pain. The average age was 73.1 years; 55.5% of the patients were male; 53.7% had diabetes, and 39.2% had arterial hypertension. Of the 54 patients subjected to an in-depth evaluation, data regarding 113 pain diagnoses were extracted, particularly related to osteoarthritis, obliterating arterial disease, and low back pain with or without radiculopathy. On the basis of these diagnoses, the pain classification according to the IASP pathophysiological definition highlighted a predominant nociceptive pain type (53.9% of all the diagnoses), followed by neuropathic (22.1%), mixed (22.1%), nociplastic (2.6%), and idiopathic (2.6%) pain. According to the IASP classification for ICD-11, the clinical diagnosis of chronic pain secondary to obliterating arterial disease and diabetes-related foot ulcers could not be assigned to any diagnostic category as a result of the lack of a specific item in the aforementioned classification.

Conclusion: This study confirmed that chronic pain is a common, burdening issue in hemodialysis patients and that it is of a prevalent nociceptive nature. Our study highlights some limitations of the last IASP ICD-11 classification, especially the lack of specific items for some pain features that are very frequent in hemodialysis patients, and not only in that population. Finally, this study underlines the importance of mutual collaboration between pain physicians and nephrologists for the well-being of patients of high clinical complexity, such as those undergoing chronic hemodialysis.

Meralgia paresthetica (MP) is a sensory mononeuropathy affecting the lateral femoral cutaneous nerve. Diagnosis is typically made clinically, often utilising multiple diagnostic aids such as imaging and electrophysiology. Upon diagnosis, the management of MP follows the standard ladder, with conservative management first line, followed by steroid injection and finally surgery. Surgery may be neurolysis or neurectomy. A literature review of the PubMed database was performed identifying 594 papers regarding MP or the lateral femoral cutaneous nerve. Following a two-stage screening process and reference searching, 34 articles were included in this review, 11 discussing diagnosis and 23 discussing management. Despite the longstanding knowledge of MP, there remains limited comprehensive research discussing its diagnosis and management. Diagnosis of MP is based on clinical examination, imaging and electrophysiology. There is no obviously superior diagnostic strategy for MP. Once that diagnosis is made, the management strategy is typical of any condition, wherein a patient will move up the intervention ladder. It is apparent that conservative management and steroid injection are both adequate in most patients. Where these strategies fail, surgical options such as decompression, radiofrequency ablation or neurectomy are suitable for the majority of remaining patients. While both neurolysis and neurectomy are described as appropriate strategies, there is a scope for discussion regarding whether one is superior. Other management strategies such as botox, acupuncture and kinesio taping may have some value, but limited research exists on these strategies and further research into these is required.

Postoperative pain significantly affects many surgical patients. While opioids are crucial for pain management, they come with unwanted side effects. Alternatives like nonsteroidal anti-inflammatory drugs, N-methyl-D-aspartate (NMDA) receptor antagonists, and regional anesthesia techniques such as nerve blocks are utilized, but these also have limitations. This underscores the need for complementary non-pharmacological interventions to enhance postoperative pain control and reduce opioid dependence. This study aimed to synthesize evidence on the efficacy of nondrug approaches for managing postoperative pain. The study examined the effects of non-pharmacological interventions such as preoperative patient education, mind-body modalities, and physical therapies. Findings suggest that these approaches can reduce pain intensity, decrease opioid consumption, and enhance recovery outcomes. The study also highlighted the pivotal role of healthcare professionals in implementing these strategies. However, it identified workload constraints and insufficient training as barriers to effective utilization in clinical practice. Integrating non-pharmacological interventions into multimodal pain management regimens can improve postoperative pain control and reduce reliance on opioids. Further research is crucial to definitively establish the efficacy of individual interventions and optimize their combined use in clinical practice. Additionally, enhanced training programs for nurses and initiatives to facilitate the implementation of these strategies are necessary for their successful adoption.

Introduction: To investigate the short-term clinical effect of transforaminal endoscopic lumbar discectomy (TELD) versus coblation nucleoplasty (CN) combined with collagenase chemonucleolysis (CCNL) in the treatment of lumbar disc herniation (LDH) with grade I degenerative spondylolisthesis.

Methods: From January 2019 to December 2020, 60 patients who had LDH with grade I degenerative spondylolisthesis were divided into two groups. Group A adopted TELD while Group B adopted CN combined with CCNL. The surgical efficacy was evaluated according to the visual analogue scale (VAS), oswestry disability index (ODI), quality of recovery-15 (QoR-15), and modified MacNab criteria. Imaging findings including lumbar lordosis (LL), segmental lordosis angle (SL), slip percentage (SP), and disc height (DH) were compared between the two groups pre-operation and at the last follow-up.

Results: VAS (back and leg), ODI, and QoR-15 were significantly decreased at each time point after operation in all groups. There were significant differences in VAS (back and leg), ODI, and QoR-15 between the two groups at 3 days post-operation (P < 0.05), VAS (leg), ODI, and QoR-15 at 3 months post-operative (P < 0.05), and QoR-15 at 6 months post-operative (P < 0.05). There was no significant difference in LL, SL, SP, and DH between the two groups at the last follow-up (P > 0.05).

Conclusion: Both the two operations can relieve the symptoms of lower back and leg pain in patients, and neither of the two operations caused further progress of lumbar spondylolisthesis. Compared with CN combined with CCNL, TELD had more significant improvement in early lower back and leg pain and shorter post-operative duration of hospitalization.

Trial registration: The trial was registered on ClinicalTrials.gov (ChiCTR2300076809).

Introduction: Single-injection pericapsular nerve group (PENG) block with ropivacaine provides clear analgesic effects in preoperative pain management for hip fractures. However, it suffers from insufficient duration, failing to meet the needs of most patients. This single-center, randomized controlled, observer-blinded trial utilizes a novel combination of liposomal bupivacaine (LB) single-injection PENG block to examine its efficacy, duration, and safety in preoperative analgesia for hip fractures, aiming to develop a new preoperative analgesic protocol.

Methods: Sixty-six patients with hip fractures received ultrasound-guided single-injection PENG block with LB or ropivacaine after admission. The primary outcome was the static and dynamic pain scores measured at 48 h post-block. Pain scores at 12, 24, 36, 60, and 72 h post-block, rescue analgesia rate, time to first opioid, additional morphine consumption, and adverse events were assessed as the secondary outcomes.

Results: LB versus ropivacaine group at 48 h post-block, with a median interquartile range (IQR) of 2 (1.0-2.0) versus 3 (2.0-3.0) at static pain score and 2 (1.75-3.0) versus 4 (4.0-5.0) at dynamic pain score. LB group had lower dynamic and static pain scores at other observation points except for the static pain score at 72 h, lower pain intensity [sum of pain intensity difference (SPID)_0-24, SPID_0-48 and SPID_0-72], longer time to first opioid, lower additional morphine consumption, and lower incidence of nausea and vomiting. No significant inter-group differences were detected in other secondary outcomes.

Conclusions: For preoperative analgesia of hip fractures, LB single-injection PENG block had a similar analgesic intensity and safety as ropivacaine but provided a longer duration of analgesia, reaching 48 h and even extending beyond 60 h, which reduced opioid consumption and extended time to the first opioid.

Trial registration: The protocol was registered in  www.chictr.org.cn  under the identifier ChiCTR2300072939.