Pain and Therapy最新文献

{"title":"Safety of Rimegepant in Adults with Migraine and Anxiety, Depression, or Using Antidepressants: Analysis of a Multicenter, Long-Term, Open-Label Study.","authors":"David Kudrow, Susan Hutchinson, Glenn C Pixton, Terence Fullerton","doi":"10.1007/s40122-024-00675-6","DOIUrl":"10.1007/s40122-024-00675-6","url":null,"abstract":"<p><strong>Introduction: </strong>Anxiety and depression are frequently associated with migraine, and antidepressant use can complicate treatment. These analyses assessed the safety and tolerability of rimegepant in participants with migraine and anxiety and/or depression, or using selective serotonin reuptake inhibitors (SSRIs) and/or other antidepressants.</p><p><strong>Methods: </strong>Data were from a phase II/III safety study of rimegepant for the acute treatment of migraine. Participants with a history of 2-14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg as needed up to once daily for up to 52 weeks. These post hoc subgroup analyses assessed safety according to self-reported history of anxiety (yes or no) or depression (yes or no), and current use of SSRIs (yes or no) or other antidepressants (yes or no).</p><p><strong>Results: </strong>Of 1800 treated participants, 23.2% (n = 417) had a self-reported history of anxiety, 23.7% (n = 426) had a self-reported history of depression, and 11.2% (n = 202) reported both anxiety and depression. A total of 10.1% (n = 181) of participants were using an SSRI, 10.8% (n = 195) were using other antidepressants, and 1.8% (n = 32) were using both. Across the subgroups with anxiety, without anxiety, with depression, without depression, using SSRIs, not using SSRIs, using other antidepressants, and not using other antidepressants, respectively, similar proportions of participants reported adverse events (67.1%, 58.4%, 62.0%, 60.0%, 64.1%, 60.0%, 66.2%, 59.8%), serious adverse events (3.6%, 2.3%, 2.8%, 2.5%, 3.3%, 2.5%, 5.1%, 2.3%), and discontinuation of rimegepant due to adverse events (4.1%, 2.2%, 3.1%, 2.5%, 5.0%, 2.4%, 3.1%, 2.6%). Numerical improvements in a variety of participant-reported outcomes were also observed at weeks 12 and 52.</p><p><strong>Conclusions: </strong>Rimegepant showed favorable safety and tolerability in adults with migraine and a history of anxiety and/or depression and with SSRI and/or other antidepressant use.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov: NCT03266588.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"237-255"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142625688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repetitive Transcranial Magnetic Stimulation: Is it an Effective Treatment for Cancer Pain?","authors":"Yanyuan Du, Yaoyuan Li, Jieqing Hu, Ruiying Fang, Yuming Liu, Liu Cai, Ying Song, Susu Ma, Jin Gao, Hanyue Zhang, Baihui Li, Hongtai Xiong, Huibo Yu, Shenglei Yang, Shuduo Zhu, Honggang Zheng","doi":"10.1007/s40122-024-00679-2","DOIUrl":"10.1007/s40122-024-00679-2","url":null,"abstract":"<p><p>Cancer is a major public health issue, with an estimated 20 million new cases and 9.7 million cancer-related deaths worldwide in 2022. Approximately 44.5% of patients experience cancer pain, significantly impacting their quality of life and causing physical and psychological burdens. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, shows potential in managing cancer pain. This review summarizes current research on rTMS for cancer pain, focusing on pain directly caused by tumors, pain from cancer treatments, postoperative pain, and cancer-related symptoms. Additionally, rTMS shows promise in improving cancer-related fatigue, anxiety, depression, and cognitive dysfunction, which can indirectly reduce cancer pain. The analgesic mechanisms of rTMS include inhibiting nociceptive signal transmission in the spinal cord, modulating hemodynamic changes in brain regions, and promoting endogenous opioid release. High-frequency stimulation of the primary motor cortex (M1) has shown significant analgesic effects, improving patients' emotional and cognitive functions and overall quality of life. rTMS has a favorable safety profile, with most studies reporting no severe adverse events. In conclusion, rTMS holds substantial potential for cancer pain management, offering a non-invasive and multifaceted therapeutic approach. Continued research and clinical application are expected to establish rTMS as an essential component of comprehensive cancer pain treatment strategies, significantly enhancing the overall well-being of patients with cancer.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"47-66"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autologous Peripheral Blood-Derived Orthobiologics for the Management of Shoulder Disorders: A Review of Current Clinical Evidence.","authors":"Ashim Gupta, Nicola Maffulli","doi":"10.1007/s40122-024-00684-5","DOIUrl":"10.1007/s40122-024-00684-5","url":null,"abstract":"<p><strong>Introduction: </strong>A multidisciplinary approach is recommended to manage shoulder pain, the third most common musculoskeletal disorder, but traditional modalities have limitations, providing only temporary symptomatic pain relief instead of targeting the underlying pathophysiology. Recently, autologous peripheral blood-derived orthobiologics (APBOs) have become popular for the management of shoulder disorders. Platelet-rich plasma (PRP) is the most frequently used APBO, but its efficacy remains disputable. Thus, the possibility of using other APBOs, such as platelet lysate (PL), autologous conditioned serum (ACS), gold-induced cytokine (GOLDIC), plasma rich in growth factors (PRGF), growth factor concentrate (GFC), autologous protein solution (APS), and hyperacute serum (HS), for the management of shoulder disorders have been considered. This review summarizes the outcomes of clinical studies involving APBOs to manage shoulder disorders.</p><p><strong>Methods: </strong>Multiple databases (PubMed, Web of Science, Embase, and Scopus) were searched employing terms for APBOs and various shoulder disorders for articles published in the English language to September 11, 2024, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.</p><p><strong>Results: </strong>Only six clinical studies fulfilled our pre-defined search and inclusion criteria. Specifically, one, two, two, and one studies involving the use of PL, ACS, PRGF, and APS, respectively, were included in this review. No clinical studies were identified involving the use of GOLDIC, GFC, and HS.</p><p><strong>Conclusions: </strong>Administration of PL, ACS, PRGF, and APS is safe and can reduce pain and improve function in patients with shoulder disorders, including rotator cuff tendinopathy, subacromial impingement syndrome, glenohumeral osteoarthritis and delayed union fracture of the clavicle. Given the dearth of relevant literature and limitations of the available studies, more prospective clinical studies, and ideally, randomized controlled trials, with extended follow-up are necessary to establish the efficacy of APBOs and to select the ideal APBO for the management of shoulder disorders.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"67-79"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and Novel Therapies for Cluster Headache: A Narrative Review.","authors":"Bruna de Freitas Dias, Christopher L Robinson, Maria Dolores Villar-Martinez, Sait Ashina, Peter J Goadsby","doi":"10.1007/s40122-024-00674-7","DOIUrl":"10.1007/s40122-024-00674-7","url":null,"abstract":"<p><p>Cluster headache (CH) is an excruciating and debilitating primary headache disorder. The prevalence is up to 1.3%, and the typical onset is around age 30. Often misdiagnosed as migraine, particularly in children, the diagnosis rate of CH has been increasing among women. CH is characterized by intense unilateral pain and autonomic symptoms, significantly impacting patients' quality of life, mental health, and productivity.Genetic associations suggest a familial risk for developing CH, with lifestyle factors also potentially playing a role. The pathophysiology involves alterations in both central and peripheral nervous system, with the hypothalamus, trigeminocervical complex, and neuropeptides such as calcitonin gene-related peptide (CGRP) being implicated.Nonpharmacological treatments focus on patient education and lifestyle modifications, while pharmacological treatments include acute therapies such as oxygen and subcutaneous or nasal sumatriptan, as well as preventive therapies like verapamil, lithium, and CGRP monoclonal antibodies. Transitional options include oral corticosteroids and greater occipital nerve injections. Emerging interventional procedures offer new avenues for managing refractory cases. Noninvasive vagal nerve stimulation and occipital nerve stimulation show promise for both acute and preventive treatment. Careful consideration of safety profiles is crucial in specific populations such as pregnant patients and children.Current treatments still leave patients highly burdened by limited efficacy and side effects. Future research continues to explore novel pharmacological targets, interventional procedures, and the potential role of psychedelics in CH management. Comprehensive, multifaceted treatment strategies are essential to improve the daily functioning and quality of life for individuals with CH.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1-19"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms and Therapeutic Potential of GPX4 in Pain Modulation.","authors":"Shiwen Fan, Kaixin Wang, Tianhao Zhang, Daling Deng, Jiwei Shen, Bowen Zhao, Daan Fu, Xiangdong Chen","doi":"10.1007/s40122-024-00673-8","DOIUrl":"10.1007/s40122-024-00673-8","url":null,"abstract":"<p><p>Pain, a complex symptom encompassing both sensory and emotional dimensions, constitutes a significant global public health issue. Oxidative stress is a pivotal factor in the complex pathophysiology of pain, with glutathione peroxidase 4 (GPX4) recognized as a crucial antioxidant enzyme involved in both antioxidant defense mechanisms and ferroptosis pathways. This review systematically explores GPX4's functions across various pain models, including neuropathic, inflammatory, low back, and cancer-related pain. Specifically, the focus includes GPX4's physiological roles, antioxidant defense mechanisms, regulation of ferroptosis, involvement in signal transduction pathways, and metabolic regulation. By summarizing current research, we highlight the potential of GPX4-targeted therapies in pain management.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"21-45"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding \"Analgesic Effectiveness of Truncal Plane Blocks in Patients Undergoing the Nuss Procedure: A Randomized Controlled Trial\".","authors":"Guanyu Yang, Qinjun Chu","doi":"10.1007/s40122-024-00682-7","DOIUrl":"10.1007/s40122-024-00682-7","url":null,"abstract":"","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"437-438"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Intraoperative Pain Management on Postoperative Delirium in Elderly Patients: A Prospective Single-Center Randomized Controlled Trial.","authors":"Yuhao Du, Jiangbing Cao, Chen Gao, Keqiang He, Sheng Wang","doi":"10.1007/s40122-024-00702-6","DOIUrl":"10.1007/s40122-024-00702-6","url":null,"abstract":"<p><strong>Introduction: </strong>Intraoperative analgesia and sedation are closely related to postoperative delirium. Depth of sedation based on bispectral index (BIS) guidance has been shown to reduce the occurrence of postoperative delirium (POD). However, the correlation between intraoperative analgesia levels and POD is unclear. The aim of this study was to investigate the effect of intraoperative analgesic management guided by the nociceptive stimulus index (NOX) on postoperative delirium.</p><p><strong>Methods: </strong>In this prospective single-center randomized controlled study, elderly patients aged 65 and above, who are scheduled to undergo unilateral total knee arthroplasty (TKA), were allocated into two groups: the routine monitoring group (group R), which solely monitored patient sedation levels using BIS; and the NOX monitoring group (group N), which monitored patient analgesic levels using NOX based on BIS-monitored sedation levels. The primary outcome was the incidence of postoperative delirium within 3 days after surgery, using the confusion assessment method (CAM).</p><p><strong>Results: </strong>From May 2022 to December 2022, a total of 240 patients were randomized; 12 were excluded because of failure to meet experimental conditions or were lost to follow-up. Patients in group N had a lower incidence rate (%) of POD on the first day compared to those in group R (8 (7%) vs 18 (16%), P = 0.041). The dosage of remifentanil administered in group N was significantly higher than that in group R (927.07 ± 268.09 vs 882.32 ± 187.91 mg, P = 0.002).</p><p><strong>Conclusions: </strong>Appropriate intraoperative analgesia guided by NOX is associated with POD. When sedation levels were consistent, the incidence of POD was significantly reduced in older patients with NOX-guided analgesic management during unilateral TKA surgery.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"387-400"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultrasound-Guided Thoracic Paravertebral Injection of Platelet-Rich Plasma for the Treatment of Thoracic Herpes Zoster-Related Pain: A Study Protocol.","authors":"Liu Wang, Xinyu Lei, Zhixuan Lan, Ruilin He, Zongbin Jiang","doi":"10.1007/s40122-024-00691-6","DOIUrl":"10.1007/s40122-024-00691-6","url":null,"abstract":"<p><strong>Background: </strong>Herpes zoster (HZ), triggered by the reactivation of the varicella-zoster virus, manifests as a painful rash known as zoster-associated pain (ZAP), which can progress to postherpetic neuralgia (PHN). This study evaluates the efficacy and safety of ultrasound-guided thoracic paravertebral injections of platelet-rich plasma (PRP) in managing acute ZAP and preventing PHN.</p><p><strong>Methods: </strong>This is a prospective, randomized, controlled, open-label, endpoint-blinded, single-center trial involving 128 participants suffering from zoster-associated pain. Participants will be randomly assigned to the PRP treatment in combination with antiviral therapy group or the antiviral therapy group at a 1:1 ratio. Pain intensity (NRS-11), quality of life (SF-12), sleep quality (PSQI), pain characteristics, skin lesion recovery, average weekly consumption of rescue analgesics, and adverse events will be assessed. Follow-up assessments will be conducted at 1, 3, 6, and 12 months post-intervention to evaluate the incidence rate of PHN, pain intensity, quality of life, sleep quality, and safety.</p><p><strong>Ethics and dissemination: </strong>Adhering to the 2013 SPIRIT statement and the Declaration of Helsinki, this study has received ethical approval from the relevant committee. Results will be disseminated through scientific journals and conferences, contributing to global data on managing ZAP.</p><p><strong>Conclusions: </strong>By comparing PRP with antiviral therapy, this trial seeks to establish a more effective treatment paradigm for reducing acute zoster-associated pain and the incidence of PHN, potentially setting a new standard in therapeutic strategies for HZ.</p><p><strong>Trial registration: </strong>This clinical trial is registered with the Chinese Clinical Trial Registry (ChiCTR) at https://www.chictr.org.cn/index.html (Registration Number: ChiCTR2400087248, Registration Date: 2024-07-23).</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"425-436"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of ERAS and Multidisciplinary Teams on Perioperative Management in Colorectal Cancer.","authors":"Qianqian Zhang, Qinfeng Sun, Junfeng Li, Xing Fu, Yuhuan Wu, Jiawei Zhang, Xia Jin","doi":"10.1007/s40122-024-00667-6","DOIUrl":"10.1007/s40122-024-00667-6","url":null,"abstract":"<p><strong>Introduction: </strong>The Enhanced Recovery After Surgery (ERAS) protocol, a comprehensive multimodal approach, aims to mitigate surgical stress, expedite recovery, and improve postoperative outcomes. Its implementation has notably advanced perioperative care in colorectal cancer surgeries. Integrating ERAS with multidisciplinary collaboration, involving surgery, anesthesia, nursing, and nutrition, may further enhance patient outcomes, making it a significant focus in clinical practice.</p><p><strong>Methods: </strong>This study assessed the effectiveness of integrating the ERAS model with multidisciplinary collaboration during the perioperative period in colorectal cancer patients. A total of 117 patients scheduled for elective surgery at Haiyan People's Hospital between August 2023 and April 2024 were randomly assigned to either a control group (n = 59), receiving traditional care, or an experimental group (n = 58), receiving ERAS-based multidisciplinary care. Key outcomes related to postoperative rehabilitation were evaluated.</p><p><strong>Results: </strong>Patients in the ERAS group demonstrated significantly shorter hospital stays, quicker catheter removal, and earlier mobilization compared to the control group (P < 0.0001 for all). Additionally, the ERAS group exhibited reduced postoperative inflammatory responses, as indicated by significantly lower interleukin-6 levels on the first postoperative day (P = 0.0247). The quality of life was significantly higher in the ERAS group (P < 0.05). Furthermore, the ERAS group incurred lower total hospitalization expenses than the control group (P = 0.0011).</p><p><strong>Conclusion: </strong>These findings confirm the benefits of the ERAS protocol in enhancing postoperative recovery in colorectal cancer surgeries. The study highlights the importance of a multidisciplinary approach in optimizing patient outcomes and reducing the burden on hospital resources.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"201-215"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Evaluation of Cyclooxygenase Inhibition Profiles Across Various NSAID Forms and Doses: Implications for Efficacy and Adverse Effects.","authors":"Kenshu Shirakawa, Masafumi Takeno, Hidekazu Kuma, Takaaki Terahara, Shigeki Yamaguchi","doi":"10.1007/s40122-024-00687-2","DOIUrl":"10.1007/s40122-024-00687-2","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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).</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>The findings explain why the transdermal formulation exerts an analgesic effect despite having a lower C_max than other diclofenac sodium formulations.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"329-338"},"PeriodicalIF":4.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142838714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}