Pain and Therapy最新文献

{"title":"Changes in Use of Migraine Medications, Healthcare Resource Utilization, and Associated Direct Costs Over 12 Months Following Initiation of Erenumab: A US Retrospective Real-World Analysis.","authors":"Robert Urman, Nicole Princic, Fiston Vuvu, Leah B Patel, Sam Oh, David Chandler, Nada Hindiyeh, Mark E Bensink","doi":"10.1007/s40122-024-00644-z","DOIUrl":"10.1007/s40122-024-00644-z","url":null,"abstract":"<p><strong>Introduction: </strong>Erenumab-aooe is approved for the preventive treatment of migraine in adults. Recent publications have evaluated migraine medication use during the 6 months after starting erenumab, but longer-term follow-up data are limited. The objective of this study was to describe 12-month medication use and changes in healthcare resource utilization (HRU) and associated direct costs among patients initiating erenumab.</p><p><strong>Methods: </strong>We identified adult patients with an erenumab claim in the Merative MarketScan Commercial and Medicare Databases from May 2018 through September 2019. Eligible patients had ≥ 12 months of continuous medical and pharmacy coverage before (pre-index period) and after (post-index period) the index date (first erenumab claim) in addition to pre-index evidence of migraine. Patients were stratified by post-index-period adherence to erenumab, defined as ≥ 80% of days covered (adherent) or < 80% of days covered (non-adherent). Outcomes were measured pre- and post-index, and differences between these periods were described.</p><p><strong>Results: </strong>Among 7528 eligible patients, the mean (standard deviation) age was 45.1 (11.4) years and 85.4% were female; 38.5% of patients were adherent to erenumab. Most patients used acute or traditional migraine-preventive medications pre-index, with reductions in use observed post-index (acute medication was used by 95.6% of patients pre-index, compared to 92.3% post-index; traditional preventive medication was used by 89.6% of patients pre-index, compared to 81.9% post-index). Reductions were observed for HRU of emergency room visits (- 3.8%) and brain- and other head-imaging studies (- 7.5%). Overall costs associated with acute and traditional preventive medications were reduced (- $764), but costs for HRU increased slightly ($76). When stratifying by adherence and combining costs for acute and traditional preventive medications and HRU, adherent patients had cost decreases (- $1947), while non-adherent patients had cost increases ($101).</p><p><strong>Conclusion: </strong>Most patients initiating erenumab had prior use of acute and traditional migraine-preventive therapies. The reduction in acute and traditional migraine-preventive medication use and HRU over the 12-month follow-up supports the long-term clinical benefits of erenumab in the real-world setting.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"1299-1313"},"PeriodicalIF":4.1,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11393376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036609","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":"Patients’ Experiences During the Long Journey Before Initiating Migraine Prevention with a Calcitonin Gene-Related Peptide (CGRP) Monoclonal Antibody (mAb)","authors":"Elizabeth Seng, Christian Lampl, Lars Viktrup, William R. Lenderking, Hayley Karn, Margaret Hoyt, Gilwan Kim, Dustin Ruff, Michael H. Ossipov, Maurice Vincent","doi":"10.1007/s40122-024-00652-z","DOIUrl":"https://doi.org/10.1007/s40122-024-00652-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Migraine is under-diagnosed and under-treated. Many people with migraine do not seek medical care, and those who do may initially receive a different diagnosis and/or be dissatisfied with provided care on their journey before treatment with a CGRP-mAb (calcitonin-gene-related-peptide monoclonal antibody).</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This is a cross-sectional, self-reported, online survey of subjects in Lilly’s Emgality^® Patient Support Program in 2022. Questionnaires collected insights into subjects’ prior experiences with migraine and interactions with healthcare professionals before receiving CGRP-mAbs.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of the 250 participants with episodic and 250 with chronic migraine, 90% were female and white with a mean age of 26.2 years (± 11.9) at diagnosis and 40.6 (± 12.0) years at survey enrollment. Many participants (71%) suspected they had migraine before diagnosis, with 31% reluctant to seek help. Of these, approximately one-third were unaware of treatment, did not think that a physician could do anything more for migraine, would not take them seriously, or were reluctant due to a previous unhelpful experience. Participants mainly received information from friends/family (47%) or the internet (28%). Participants initially sought treatment due to an increase in migraine frequency (77%), attacks interfering with work or school (75%), or increased pain intensity (74%). Subjects saw a mean of 4.1 (± 4.3) healthcare providers before migraine diagnosis, and 20% of participants previously received a different diagnosis. Participants reported migraine causes included stress/anxiety/depression (42%), hormonal changes (30%), nutrition (20%), and weather (16%). Acute treatment of migraine included prescription (82%) and over-the-counter (50%) medications, changes in nutrition (62%), adjusting fluid intake (56%), and relaxation techniques (55%). Preventive medications included anticonvulsants (61%), antidepressants (44%), blood pressure-lowering medications (43%), and botulinum toxin A injections (17%). Most discontinuations were due to lack of efficacy or side effects.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>People with migraine describe reluctance in seeking health care, and misunderstandings seem common especially in the beginning of their migraine journey.</p><p>Graphical abstract available for this article.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"12 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence of the Safety and Effectiveness of Atogepant Added to OnabotulinumtoxinA for the Preventive Treatment of Chronic Migraine: A Retrospective Chart Review","authors":"Andrew M. Blumenfeld, Laszlo Mechtler, Lisa Cook, Christopher Rhyne, Brian Jenkins, Olivia Hughes, Brett Dabruzzo, Aubrey Manack Adams, Merle Diamond","doi":"10.1007/s40122-024-00649-8","DOIUrl":"https://doi.org/10.1007/s40122-024-00649-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1 month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs).</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7 years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (<i>n</i> = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (<i>N</i> = 31) and second (<i>N</i> = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3 months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6 months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"42 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain Characteristics of the Posterior Longitudinal Ligament in Percutaneous Endoscopic Lumbar Discectomy and its Significance: A Retrospective Study","authors":"Kaining Zhang, Yun Yang, Wen Yu, Yubin Qi, Yanjun Ren, Yingguang Wu, Wa Shan, Fengxiang Zhu, Feifei Chen","doi":"10.1007/s40122-024-00656-9","DOIUrl":"https://doi.org/10.1007/s40122-024-00656-9","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin–eosin (HE) staining and immunohistochemistry.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (<i>P</i> &lt; 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (<i>P</i> &lt; 0.0001).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"68 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142254628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study","authors":"Jamie Burgess, Anne Marshall, Leandros Rapteas, David Riley, Kohei Matsumoto, Cheng Boon, Alia Alchawaf, Maryam Ferdousi, Rayaz A. Malik, Andrew Marshall, Stephen Kaye, David Gosal, Bernhard Frank, Uazman Alam","doi":"10.1007/s40122-024-00646-x","DOIUrl":"https://doi.org/10.1007/s40122-024-00646-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (<i>p</i> &lt; 0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all <i>p</i> &lt; 0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: <i>p</i> = 0.002 and <i>p</i> = 0.003; pressure: both <i>p</i> &lt; 0.001) and WUR (both <i>p</i> &lt; 0.001). FMS participants exhibited reduced corneal nerve fibre density (<i>p</i> = 0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all <i>p</i> &lt; 0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Participants with SFP, in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"116 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Conditioned Pain Modulation in Trigeminal Neuralgia Patients","authors":"Yu Zhang, Yiyuan Luo, Qixing Wu, Mingming Han, Haitao Wang, Fang Kang","doi":"10.1007/s40122-024-00654-x","DOIUrl":"https://doi.org/10.1007/s40122-024-00654-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Conditioned pain modulation (CPM) is a quantitative estimation of the capacity for endogenous pain modulation. Reduced CPM enables chronic painful event development or exacerbates pre-existing pain symptoms. Emerging reports indicate that patients with trigeminal neuralgia (TN) have dysregulated endogenous pain modulation. Transauricular vagus nerve stimulation (taVNS) is known to alleviate both acute and chronic pain symptoms. Its role in modulation or management of TN remains unknown. Here, we evaluated the taVNS efficacy in modulating CPM among TN patients. Conclusions from this investigation may facilitate establishment of novel non-invasive adjunctive approaches to treating TN patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>All research work was conducted at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). In all, we recruited 62 study participants, 31 TN patients and 31 healthy volunteers, for a 2-day experimental test. At the beginning of the experiment (Day 1), all subjects received 30 min of active taVNS. On Day 2, they received sham taVNS with the same duration and intensity. Meanwhile, technicians documented participant pressure pain thresholds (PPT) and CPM values at baseline, and at 15 and 30 min post-active or sham taVNS.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A 30-min active taVNS exposure substantially elevated the PPT and CPM effect (<i>P</i> &lt; 0.05) among TN patients, and we also observed a notable rise in the PPT and CPM effect (<i>P</i> &lt; 0.05) among healthy controls. Additionally, there were no serious adverse events from the administered treatment.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Exposure to 30 min of active taVNS strongly augmented the CPM effect and elevated the PPT among TN patients and healthy controls. These effects were not observed with sham stimulation. Despite the limitations inherent to survey studies, such as duration and compliance biases, we consider that taVNS is a promising, safe, and cost-effective therapy. In future investigations, we recommend assessment of long-term taVNS application and its effects on CPM and clinical pain.</p><h3 data-test=\"abstract-sub-heading\">Trial Registration</h3><p>ChiCTR2300078673 (www.Chictr.org.cn).</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"1 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol","authors":"Miguel A. Zuqui-Ramírez, Victor M. Belalcazar-López, Adelfia Urenda-Quezada, Alejandro González-Rebatu y González, José G. Sander-Padilla, Laura A. Lugo-Sánchez, Ileana C. Rodríguez-Vázquez, Kevin F. Rios-Brito, María M. Arguedas-Núñez, Emmanuel Canales-Vázquez, Jorge González-Canudas","doi":"10.1007/s40122-024-00653-y","DOIUrl":"https://doi.org/10.1007/s40122-024-00653-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (<i>n</i> = 61) or paracetamol/tramadol TID (<i>n</i> = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [<i>p</i> = 0.054, CI 95% − 0.648 (− 0.010 to 1.306)] and 5 days (<i>p</i> = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [<i>p</i> = 0.008, CI 95% 0.241 (0.061–0.421)]. An improvement in LBP’s disability to perform activities of daily routine (Oswestry and Roland–Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%).</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence.</p><h3 data-test=\"abstract-sub-heading\">Trial registration</h3><p>ClinicalTrials.gov identifier, NCT04968158.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"51 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Benefits and Safety of Medical Cannabis Products: A Narrative Review on Natural Extracts","authors":"Gérard Mick, Pascal Douek","doi":"10.1007/s40122-024-00643-0","DOIUrl":"https://doi.org/10.1007/s40122-024-00643-0","url":null,"abstract":"<p>Interest in medical cannabis and cannabis-based medicinal products (CBMPs) has increased greatly in recent years. Two cannabinoids are of principal importance; delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive component, and also cannabidiol (CBD), considered non-intoxicating. Each has distinct mechanisms of action and different therapeutic potentials. CBMPs differ in their ∆9-THC and CBD components; predominantly ∆9-THC, balanced formulations with equivalent ∆9-THC and CBD elements, and CBD-predominant products. In this narrative review, we evaluate the published evidence for the clinical benefits of CBMPs and overall benefits in well-being. We also review the overall safety profile and discuss the potential for dependence with CBMPs. Evidence can be drawn from a wide range of randomized and other controlled studies and from observational real-world studies. Most data from observational registry studies are supportive of ∆9-THC-based products (∆9-THC-predominant or balanced CBMPs) in the management of chronic neuropathic pain. Balanced products are also effective in reducing spasticity in multiple sclerosis. Most CBMPs show benefit in providing symptomatic benefits in reducing anxiety, nausea, and in improving sleep, but the place of specific products is more subtle, and choice guided by specific circumstances. Symptomatic improvements are accompanied by improved quality of life and well-being. Safety data indicate that CBMPs are generally well tolerated in most patients without specific contraindications. The majority of adverse effects are non-serious, and transient; most are principally associated with ∆9-THC and are dose-dependent. In contrast to recreational cannabis use, there is little evidence from clinical studies that CBMPs have any potential for dependence.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":"177 1","pages":""},"PeriodicalIF":4.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141881976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain.","authors":"Xiaohui Guo, Yang Yu, Yongbo Zhang, Li Sun, Yufeng Li, Bing Song, Li Hang, Masayuki Baba, Yosuke Wasaki, Kunika Kikumori, Emiko Murayama","doi":"10.1007/s40122-024-00617-2","DOIUrl":"10.1007/s40122-024-00617-2","url":null,"abstract":"<p><strong>Introduction: </strong>There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce.</p><p><strong>Methods: </strong>This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs).</p><p><strong>Results: </strong>Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group.</p><p><strong>Conclusions: </strong>Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier, NCT04094662.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"937-952"},"PeriodicalIF":4.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420331","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 Role of Astrocytes in Migraine with Cortical Spreading Depression: Protagonists or Bystanders? A Narrative Review.","authors":"Meng-Fan Yang, Dong-Xue Ren, Xue Pan, Chang-Xin Li, Sui-Yi Xu","doi":"10.1007/s40122-024-00610-9","DOIUrl":"10.1007/s40122-024-00610-9","url":null,"abstract":"<p><p>Cortical spreading depression (CSD) is a slow wave of cortical depolarization closely associated with migraines with an aura. Previously, it was thought that CSD depolarization was mainly driven by neurons, with characteristic changes in neuronal swelling and increased extracellular potassium (K⁺) and glutamate. However, the role of astrocytes, a member of the neurovascular unit, in migraine with CSD has recently received increasing attention. In the early stages of CSD, astrocytes provide neurons with energy support and clear K⁺ and glutamate from synaptic gaps. However, in the late stages of CSD, astrocytes release large amounts of lactic acid to exacerbate hypoxia when the energy demand exceeds the astrocytes' compensatory capacity. Astrocyte endfoot swelling is a characteristic of CSD, and neurons are not similarly altered. It is primarily due to K⁺ influx and abnormally active calcium (Ca²⁺) signaling. Aquaporin 4 (AQP-4) only mediates K⁺ influx and has little role as an aquaporin. Astrocytes endfoot swelling causes perivascular space closure, slowing the glymphatic system flow and exacerbating neuroinflammation, leading to persistent CSD. Astrocytes are double-edged swords in migraine with CSD and may be potential targets for CSD interventions.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":"679-690"},"PeriodicalIF":4.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11255162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140922527","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}