Journal of Headache and Pain最新文献

{"title":"The link between spreading depolarization and innate immunity in the central nervous system.","authors":"Kadir Oguzhan Soylu, Muge Yemisci, Hulya Karatas","doi":"10.1186/s10194-024-01938-5","DOIUrl":"https://doi.org/10.1186/s10194-024-01938-5","url":null,"abstract":"<p><p>Spreading depolarization (SD) is a complex event that induces significant cellular stress in the central nervous system, leading to a robust inflammatory response without causing cell death in healthy tissues which may be called as neuro-parainflammation. Research has established a clear link between SD and the activation of pro-inflammatory pathways, particularly through the release of cytokines like interleukin-1β and tumor necrosis factor-α, and the involvement of inflammatory mediators such as cyclooxygenase-2 and high mobility group box 1 (HMGB1). Mechanistically, the opening of pannexin-1 (Panx1) channels and the activation of the (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome play critical roles in this process, facilitating the release of inflammatory signals that can exacerbate conditions like migraine. Furthermore, the interplay between neurons and glial cells, particularly astrocytes and microglia, underscores the intricate nature of neuroinflammation triggered by SD. Importantly, these findings indicate that these inflammatory processes may also have systemic implications, affecting immune responses beyond the central nervous system. Overall, this body of work highlights the need for further exploration of the mechanisms underlying SD-induced inflammation and potential therapeutic targets to mitigate neuroinflammatory disorders. Inflammation extends beyond the central nervous system to peripheral structures, including the meninges and trigeminovascular system, which are critical for headache initiation. Genetic factors, particularly familial hemiplegic migraine (FHM), exacerbate neuroinflammatory responses to SD, leading to increased susceptibility and prolonged headache behaviors. Collectively, these findings underscore the complex cellular interactions and innate inflammatory processes underlying SD and their relevance to migraine mechanisms, suggesting potential avenues for therapeutic intervention.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"25"},"PeriodicalIF":7.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epidemiology of clinically significant migraine in Israel: a retrospective database study.","authors":"A Shifrin, E Domany, M Tirosh, D Davidovici, S Vinker, I Forschner, A Israel","doi":"10.1186/s10194-025-01961-0","DOIUrl":"https://doi.org/10.1186/s10194-025-01961-0","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies on migraine are valuable for tracking disease trends, identifying risk factors, and informing treatment strategies. This study assessed the prevalence and annual incidence of clinically significant migraine in Israel from 2017 to 2022, with analyses stratified by age, sex, socioeconomic status, and district. Additionally, we compared relevant characteristics between adult migraine and non-migraine members of Leumit Healthcare Services (LHS), a national health provider in Israel.</p><p><strong>Methods: </strong>This retrospective study used LHS electronic health records to evaluate migraine prevalence and annual incidence from 2017 to 2022 among adult LHS members. Clinically significant migraine patients were identified using stringent criteria, including repeated diagnostic codes for migraine, confirmation by a neurologist, or the use of migraine-specific therapies. Each migraine patient was matched 1:1 with a control individual of similar age, sex, socioeconomic status, and ethnic background.</p><p><strong>Results: </strong>The prevalence of clinically significant migraine increased from 4.5% in 2017 to 5.2% in 2022, with significantly higher rates in women compared to men (8% vs. 2.4% in 2022). The mean age of migraine patients was 46.8 years in 2022. The annual incidence of migraine in 2022 was 43 per 10,000 individuals over 18, with approximately 75% of new cases occurring in women, with a mean age of 36.5 years. The annual incidence of migraine slightly decreased over the period. Approximately two-thirds of new patients were diagnosed by neurologists, with only 19% diagnosed by family physicians. Compared to a matched control population, migraine patients showed a higher prevalence of low body mass index (BMI) and higher diastolic blood pressure (BP). Additionally, distinct differences in laboratory findings were observed among migraine patients, notably lower glucose and hemoglobin A1c levels, lower rate of microalbuminuria, with higher hemoglobin, which may be associated with migraine pathophysiology.</p><p><strong>Conclusion: </strong>This study provides a detailed epidemiological and clinical profile of patients with clinically significant migraine in LHS from 2017 to 2022. Notable trends include higher rates of migraine among patients with lower BMI, higher diastolic BP, lower glucose, and higher hemoglobin, suggesting potential modifiable risk factors.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"24"},"PeriodicalIF":7.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shift from chronic to episodic migraine frequency in a long-term phase 3 study of galcanezumab.","authors":"Hans-Christoph Diener, Kathleen A Day, Sarah Lipsius, Sheena K Aurora, Nada A Hindiyeh, Holland C Detke","doi":"10.1186/s10194-025-01956-x","DOIUrl":"https://doi.org/10.1186/s10194-025-01956-x","url":null,"abstract":"<p><strong>Background: </strong>Chronic migraine (CM) is a highly disabling form of migraine in which patients have ≥ 15 headache days per month, of which at least 8 have the features of migraine. Galcanezumab is a monoclonal antibody to calcitonin gene-related peptide which is approved for the preventive treatment of migraine. Ability to convert patients from chronic migraine frequency to episodic migraine (EM) frequency is a clinically relevant and desirable outcome when prescribing preventive treatments to patients with CM.</p><p><strong>Methods: </strong>Patients aged 18-65 years with an ICHD-3β diagnosis of CM were randomized 2:1:1 to receive monthly injections of placebo (N = 558), galcanezumab 120 mg with a 240-mg loading dose (N = 278), or galcanezumab 240 mg (N = 277) during a 3-month double-blind period of the phase 3 REGAIN trial. Patients could subsequently enter a 9-month open-label extension in which they received galcanezumab 120 mg or 240 mg/month per investigator's discretion. In this post-hoc analysis, we assessed the percentages of patients who shifted to EM (< 8 migraine headache days or < 15 headache days/month), low frequency EM (LFEM; <8 migraine headache days/month), and very low frequency EM (VLFEM; <4 migraine headache days/month) for at least 3 consecutive months. Double-blind percentage comparisons versus placebo represent modeled estimates from raw rates.</p><p><strong>Results: </strong>At baseline, patients had a mean of 19.4 migraine headache days per month (SD = 4.5) and 21.4 headache days per month (SD = 4.1). During the 3-month double-blind treatment period, a greater percentage of galcanezumab-treated patients shifted to EM frequency and maintained it across all 3 months (31.5%) than did placebo-treated patients (19.8%, p < 0.001). Among galcanezumab-treated patients across the entire 12-month trial, 65.1% shifted from CM to EM frequency, with 44.2% shifting to LFEM and 21.5% shifting to VLFEM for ≥ 3 consecutive months. Proportions of patients shifting from CM to EM frequency for ≥ 3 consecutive months and until last patient visit were: 55.0% to EM; 33.4% to LFEM; 13.9% to VLFEM.</p><p><strong>Conclusion: </strong>These results suggest that galcanezumab helped a majority of patients convert from chronic to episodic migraine frequency over the course of this 12-month study.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov NCT02614261, first registered November 25, 2015.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"26"},"PeriodicalIF":7.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the association between statins use or HMG-CoA reductase inhibition and migraine: a systematic review and meta-analysis.","authors":"Hamdy A Makhlouf, Amr K Hassan, Nereen A Almosilhy, Ahmed S A Osman, Shrouk Ramadan, Moaz Elsayed Abouelmagd","doi":"10.1186/s10194-025-01957-w","DOIUrl":"https://doi.org/10.1186/s10194-025-01957-w","url":null,"abstract":"<p><strong>Background: </strong>Statins or 3‑hydroxy‑3‑methyl‑glutarylcoenzyme A (HMG‑CoA) reductase inhibitors are medications that act by reducing the cholesterol content of liver cells Moreover, statins have been found to improve endothelial function and reduce vascular wall inflammation. A growing body of research suggests that statins are associated with less risk of migraine, and they can be used to treat symptoms. However, the evidence has been inconclusive, so we aim to investigate the nature and strength of the effect of statins on the prevention and prophylaxis of migraines.</p><p><strong>Methods: </strong>We conducted a comprehensive systematic search across multiple electronic databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, from inception until October 2024, to include studies on the association between statins use and migraine. The outcomes of interest involved the association of the HMG-CoA reductase gene with the risk of migraine, as well as the association and efficacy of statins in migraine patients.</p><p><strong>Results: </strong>Thirteen studies were included in our systematic review. Mendelian Randomization (MR) studies revealed that expression of HMGCR was associated with an increased risk of migraine with odds ratio (OR) ranging from 1.38 to 1.55 (P < 0.001). Three observational studies investigating the relationship between statins and migraine risk demonstrated a protective effect, with odds ratios ranging from 0.73 to 0.94 (P < 0.001). The findings suggest a significant reduction in overall migraine risk, particularly for migraines with aura and in patients with higher vitamin D levels. Meta-analysis of randomized controlled trials (RCTs) showed that statins significantly reduced monthly migraine frequency (MD= -3.16, 95%CI= [-5.79, -0.53]; p = 0.02, I2 = 79%; P = 0.03). RCTs supported the efficacy of statins in reducing migraine frequency, days, and intensity compared to placebo.</p><p><strong>Conclusions: </strong>Statins, already well-established for cardiovascular benefits, emerge as a promising dual-purpose therapy for many neurological disorders. The association between the HMGCR gene and increased migraine risk, coupled with the possible efficacy of statins in reducing migraine frequency, may open new avenues for migraine prophylaxis. However, the variability in study design hinders definitive conclusions, so larger studies with longer follow-ups are required to ascertain both findings.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"23"},"PeriodicalIF":7.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fitness-to-work considerations in the paradigmatic pain condition of headache disorder.","authors":"Xiangning Fan, Ellina Lytvyak, Charl Els, Sebastian Straube","doi":"10.1186/s10194-025-01960-1","DOIUrl":"10.1186/s10194-025-01960-1","url":null,"abstract":"<p><p>Headache disorders are common, including in the working population. Clinicians caring for patients with headache need to be aware of work-related factors as potential causes or triggers of headache disorders, and consider the impact of headache on fitness-to-work, especially in safety-sensitive and decision-critical roles. Such fitness-to-work determination should include individualized consideration of the nature of the headache disorder itself, the pattern of the headache, the impact of sleep deprivation on the headache as it relates to fitness to do shiftwork, medication and substance side effects, fitness-to-work implications of associated medical or psychiatric conditions, and the potential of symptom feigning or malingering for secondary gain. As clinicians often struggle with fitness-to-work determinations, a structured approach to fitness-to-work assessments in headache conditions and other pain conditions would improve clarity for clinicians and increase the quality of care provided to patients, with potential benefits for workplace safety and policy in this arena as well.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"21"},"PeriodicalIF":7.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting substance P in migraine: a methodological approach inspired by anti-CGRP and anti-PACAP success.","authors":"Lanfranco Pellesi, Lars Edvinsson","doi":"10.1186/s10194-025-01959-8","DOIUrl":"10.1186/s10194-025-01959-8","url":null,"abstract":"<p><p>Substance P, previously dismissed as a therapeutic target for migraine due to the failure of neurokinin-1 receptor antagonists, warrants renewed attention. Building on the success of therapies targeting the calcitonin gene-related peptide (CGRP) system and pituitary adenylate cyclase-activating peptide (PACAP) in migraine prevention, which highlight the importance of targeting peptides, this proposal reexamines substance P as a mediator in migraine pathophysiology. Using an established methodological framework, migraine-inducing properties of substance P can be evaluated through randomized, double-blind, placebo-controlled crossover studies involving healthy volunteers and individuals with a history of migraine. This approach aims to establish proof of concept for substance P's role in migraine, laying the groundwork for investigations with animal and cell-based models and advancing the development of innovative treatments for patients refractory to current therapies.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"22"},"PeriodicalIF":7.3,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of proton pump inhibitor (PPI) use on migraine - a critical review.","authors":"Viktoria Tischler-Strasser, Irma Burdiladze, Goncalo Cabral, Esme Ekizoglu, Olga Grodzka, Keshet Pardo, Patryk Sochan, Laura Zaunandra, Antoinette MaassenVanDenBrink, Christian Lampl","doi":"10.1186/s10194-025-01954-z","DOIUrl":"10.1186/s10194-025-01954-z","url":null,"abstract":"<p><strong>Background: </strong>Proton pump inhibitor (PPI) drugs are widely used and are among the most significant achievements of modern pharmacology. Their primary purpose is treating and preventing gastric acid-related disorders. Migraine and PPI intake are prevalent, and many people are affected by both. In the last few years, a potential link between PPI intake and the development of headaches-especially migraine-has come to increased attention. In this review, we critically examine the scientific data concerning the co-occurrence of these two entities.</p><p><strong>Findings: </strong>There seems to be a possible link between the use of PPIs and the occurrence of headache, especially migraine, suggesting a pathophysiological connection on several levels. Moreover, PPI use is only partially without side effects, even if these may not occur immediately. Whether the relation is causative or merely co-existential is currently not yet clear. The influence of genetics, environment, gut microbiome, medication intake and evolution of headache is multidirectional.</p><p><strong>Conclusion: </strong>A relation between the prevalence of migraine and the use of PPIs on a population and personal level seems likely. Although PPIs have many advantages, they should be prescribed with caution, especially in patients who suffer from headaches and migraine. In this narrative review, we aim to critically evaluate existing data and offer a potential approach to accurately identify any connections and interactions, leading to a better understanding of how these conditions may influence each other.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"20"},"PeriodicalIF":7.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Filling the data gap on CGRP mAb therapy in low- to middle-income countries in Southeast Asia: insights from a real-world study in Thailand.","authors":"Prakit Anukoolwittaya, Akarin Hiransuthikul, Thanakit Pongpitakmetha, Sekh Thanprasertsuk, Wanakorn Rattanawong","doi":"10.1186/s10194-025-01962-z","DOIUrl":"10.1186/s10194-025-01962-z","url":null,"abstract":"","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"19"},"PeriodicalIF":7.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Headache after pediatric traumatic brain injury: a comparison between a post-acute sample of children and adolescents and general population.","authors":"Marina Zeldovich, Leonie Krol, Katrin Cunitz, Christian Auer, Daniel Pinggera, Victoria Schön, Philipp Geiger, Joachim Suss, Inga K Koerte, Emilie Isager Howe, Nada Andelic, Anna Buchheim, Matthias Gondan, Nicole von Steinbüchel","doi":"10.1186/s10194-025-01951-2","DOIUrl":"10.1186/s10194-025-01951-2","url":null,"abstract":"<p><strong>Background: </strong>Headache is one of the most common post-concussion symptoms following pediatric traumatic brain injury (TBI). To better understand its impact on young individuals, this study aims to investigate the prevalence of headache in a German-speaking post-acute pediatric TBI sample and compare it with the general population. In addition, factors associated with the development of pediatric post-TBI headache are investigated to improve the understanding of this condition.</p><p><strong>Methods: </strong>A post-acute sample (3 months up to 10 years post-injury) comprising N = 463 children and adolescents aged 8 to 17 years from the TBI sample and N = 463 individuals from the general population matched for gender, age, and health status were included in the study. The Postconcussion Symptom Inventory (PCSI) item assessing headache was used as the outcome variable. Logistic regression was used to examine the association between the risk of developing headache and sociodemographic and health-related factors.</p><p><strong>Results: </strong>Slightly less than half of the participants reported the presence of headache (TBI sample: 46%; matched controls: 44%). Compared with matched controls, the odds of headache in the TBI sample were not significantly different (OR = 1.09, 95% CI 0.85 to 1.4, p = 0.49). The association between PCSI symptoms was generally stronger in adolescents than in children and in the matched controls than in the TBI sample. In the TBI sample, the probability of reporting headache increased with age.</p><p><strong>Conclusions: </strong>The results of this study suggest that the prevalence of headache in the post-acute phase of pediatric TBI is not significantly different from that in the matched non-TBI population, indicating good recovery from injury. However, due to its high prevalence, follow-up screening for this common TBI symptom, especially in adolescents, may be helpful to prevent further chronification.</p><p><strong>Trial registration: </strong>The study is retrospectively registered in German Clinical Trials Register and in International Clinical Trials Registry Platform (ID DRKS00032854).</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"15"},"PeriodicalIF":7.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased TSPO alleviates neuropathic pain by preventing pyroptosis via the AMPK-PGC-1α pathway.","authors":"Baolong Li, Kaiming Yu, Xiongyao Zhou, Jialu Sun, Le Qi, Weiye Li, Tuo Yang, Weizhen Li, Ningning Wang, Xiaosong Gu, Shusen Cui, Rangjuan Cao","doi":"10.1186/s10194-025-01953-0","DOIUrl":"10.1186/s10194-025-01953-0","url":null,"abstract":"<p><p>Neuropathic pain poses a significant clinical challenge, largely due to the incomplete understanding of its molecular mechanisms, particularly the role of mitochondrial dysfunction. Bioinformatics analysis revealed that pyroptosis and inflammatory responses induced by spared nerve injury (SNI) in the spinal dorsal horn play a critical role in the initiation and persistence of neuropathic pain. Among the factors involved, TSPO (translocator protein) emerged as a key regulator. Our experimental findings showed that TSPO expression was upregulated during neuropathic pain, accompanied by mitochondrial dysfunction, specifically manifested as impaired mitochondrial biogenesis, disrupted mitochondrial dynamics (including insufficient expression of mitochondrial biogenesis and fusion-related proteins, as well as significantly increased expression of fission-related proteins), and activation of pyroptosis. Pharmacological upregulation of TSPO, but not its downregulation, effectively alleviated SNI-induced pain hypersensitivity, improving mitochondrial function and reducing pyroptosis. Immunofluorescence staining confirmed that TSPO was primarily localized in astrocytes, and its expression mirrored the protective effects on mitochondrial health and pyroptosis prevention. PCR array analysis suggested a strong association between TSPO and the mitochondrial regulation pathway AMPK-PGC-1α. Notably, inhibition of AMPK-PGC-1α abolished TSPO effects on mitochondrial balance and pyroptosis suppression. Furthermore, Mendelian randomization analysis of GWAS data indicated that increased TSPO expression was linked to pain relief. Through drug screening, molecular docking, and behavioral assays, we identified zopiclone as a promising TSPO-targeting drug for pain treatment. In summary, this study enhances our understanding of the molecular interplay between TSPO, mitochondrial health, and neuropathic pain, highlighting TSPO as a potential therapeutic target for pain management.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"16"},"PeriodicalIF":7.3,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}