Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-02-03DOI: 10.1007/s43440-025-00700-1
Guangli Wang, Yuling Wang, Changhao Jin, Xiaodan Sun
{"title":"Off-label use of anlotinib in malignancies' treatment: efficacy and management of adverse reactions.","authors":"Guangli Wang, Yuling Wang, Changhao Jin, Xiaodan Sun","doi":"10.1007/s43440-025-00700-1","DOIUrl":"10.1007/s43440-025-00700-1","url":null,"abstract":"<p><p>Anlotinib is a novel small-molecule multi-target tyrosine kinase inhibitor (TKIs) independently developed in China, it possesses the functions of inhibiting tumor angiogenesis and suppressing tumor growth. Anlotinib has achieved notable therapeutic effects in approved indications for advanced non-small cell lung cancer, soft tissue sarcoma, small cell lung cancer, and medullary thyroid carcinoma. Additionally, with unanimous expert consensus, it has been used off-label in various other tumors, yielding favorable outcomes. This article reviews the efficacy and common adverse reactions, as well as their management, of off-label use of anlotinib in various malignant tumors.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"392-408"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-01-14DOI: 10.1007/s43440-025-00695-9
Krishna K Gollapelli, Ivan Krizan, Bhuvanachandra Bhoopal, Naresh Damuka, Carson Moriarty, Mack Miller, Kiran K Solingapuram Sai, Robert W Gould
{"title":"[<sup>11</sup>C]MK-6884 PET imaging reveals lower M<sub>4</sub> muscarinic acetylcholine receptor availability following cocaine self-administration in male rats.","authors":"Krishna K Gollapelli, Ivan Krizan, Bhuvanachandra Bhoopal, Naresh Damuka, Carson Moriarty, Mack Miller, Kiran K Solingapuram Sai, Robert W Gould","doi":"10.1007/s43440-025-00695-9","DOIUrl":"10.1007/s43440-025-00695-9","url":null,"abstract":"<p><strong>Background: </strong>Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M<sub>4</sub> mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD. However, it is unclear how cocaine exposure affects M<sub>4</sub> mAChR expression or distribution.</p><p><strong>Objectives: </strong>To evaluate the effects of cocaine self-administration on M<sub>4</sub> mAChR availability using [<sup>11</sup>C]MK-6884 in vivo PET imaging in rats that self-administered cocaine (cocaine SA) or sucrose pellets (control).</p><p><strong>Methods: </strong>Sprague-Dawley rats self-administered cocaine or sucrose pellets for 15 days under 2-h or 4-h sessions followed by PET imaging with [<sup>11</sup>C]MK-6884, a radiolabeled M<sub>4</sub> selective positive allosteric modulator to determine the effects of cocaine on [<sup>11</sup>C]MK-6884 standard uptake values with cerebellum as reference (SUVr).</p><p><strong>Results: </strong>Cumulative cocaine intake ranged between 324 and 776 mg/kg. Cocaine self-administration was associated with significantly lower [<sup>11</sup>C]MK-6884 SUVrs in the cortex, hippocampus, and striatum compared to cocaine-naive rats, with a negative correlation between radiotracer SUVrs and cocaine intake in the hippocampus.</p><p><strong>Conclusions: </strong>These results suggest that cocaine self-administration decreases M<sub>4</sub> mAChR availability, providing further support for pursuing activation/enhancement of M<sub>4</sub> mAChR function as a viable pharmacotherapeutic approach for CUD.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"532-541"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11911261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2024-12-23DOI: 10.1007/s43440-024-00689-z
Aleksandra Wisłowska-Stanek, Michał Jarkiewicz, Dagmara Mirowska-Guzel
{"title":"Rebound effect, discontinuation, and withdrawal syndromes associated with drugs used in psychiatric and neurological disorders.","authors":"Aleksandra Wisłowska-Stanek, Michał Jarkiewicz, Dagmara Mirowska-Guzel","doi":"10.1007/s43440-024-00689-z","DOIUrl":"10.1007/s43440-024-00689-z","url":null,"abstract":"<p><p>Sudden cessation of the drug can cause withdrawal syndrome, discontinuation syndrome, or rebound effect. The common feature of these phenomena is a quick onset, usually limited duration depending on the drug's half-life and remission after restarting the therapy. They are characterized by varying clusters of somatic, autonomic, and psychiatric symptoms. Originally withdrawal syndrome was described for drugs with addictive properties such as barbiturates or benzodiazepines. On the other hand sudden abrupt of antidepressants or antipsychotics may cause discontinuation symptoms including movement or sensory disturbances, sleep disturbances, and hyperarousal but generally of less severity comparing to withdrawal syndrome. The aforementioned syndromes are physiologically based on the predominance of cellular counter-regulations as an effect of the sudden abrupt of a regularly taken medication. Classically the pathogenesis of withdrawal syndrome, based on physical dependence, results in life-threatening, long-lasting manifestations such as, seizures and delirium, different from the treated disease. In turn, these symptoms are not typical for discontinuation syndrome which is not considered as serious and usually spontaneously resolving. In turn, the rebound effect is clinically characterized by the relapse of the disease symptoms that are controlled by medication, but of greater severity than those before treatment.In the current review, we describe withdrawal and discontinuation syndromes associated with selected drugs used in psychiatry and neurology, risk factors, and recommendations for diminishing syndrome occurrence. Knowledge of their pathogenesis and symptoms resulting from drug discontinuation may be helpful in syndrome management and expectantly reduces the risk of diagnostic and therapeutic errors.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"303-314"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Exploring melatonin's signalling pathways in the protection against age-related skin deterioration.","authors":"Maryam Taheri, Farnoosh Seirafianpour, Amirali Fallahian, Azam Hosseinzadeh, Russel J Reiter, Saeed Mehrzadi","doi":"10.1007/s43440-025-00699-5","DOIUrl":"10.1007/s43440-025-00699-5","url":null,"abstract":"<p><p>Melatonin, renowned for regulating sleep-wake cycles, also exhibits notable anti-aging properties for the skin. Synthesized in the pineal gland and various tissues including the skin, melatonin's efficacy arises from its capacity to combat oxidative stress and shield the skin from ultraviolet (UV)-induced damage. Moreover, it curbs melanin production, thereby potentially ameliorating hyperpigmentation. The presence of melatonin receptors in diverse skin cell types and its documented ability to enhance skin tone, hydration, and texture upon topical administration underscores its promise as an anti-aging agent. Melatonin's protective effects likely emanate from its multifaceted characteristics, encompassing antioxidant, anti-inflammatory, and immunomodulatory functions, as well as its influence on collagen synthesis and mitochondrial activity. Chronic inflammation and oxidative stress initiate a detrimental feedback loop. Reactive oxygen species (ROS), notorious for damaging cellular structures, provoke immune responses by oxidizing vital molecules and activating signaling proteins. This triggers heightened expression of inflammatory genes, perpetuating the cycle. Such dysregulation significantly compromises the body's resilience against infections and other health adversities. This study embarks on an exploration of the fundamental signaling pathways implicated in skin aging. Furthermore, it delves into the therapeutic potential of melatonin and its anti-aging attributes within the realm of skin health.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"375-391"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-01-14DOI: 10.1007/s43440-024-00690-6
Jairo Izidro Rossetti Navarro Júnior, Rafaela Aires, Thiago Antonio de Sousa Cutrim, Elisardo Corral Vasquez, Thiago Melo Costa Pereira, Bianca Prandi Campagnaro
{"title":"Efficacy of probiotic adjuvant therapy in women with major depressive disorder: insights from a case series study.","authors":"Jairo Izidro Rossetti Navarro Júnior, Rafaela Aires, Thiago Antonio de Sousa Cutrim, Elisardo Corral Vasquez, Thiago Melo Costa Pereira, Bianca Prandi Campagnaro","doi":"10.1007/s43440-024-00690-6","DOIUrl":"10.1007/s43440-024-00690-6","url":null,"abstract":"<p><strong>Background: </strong>The therapeutic targeting of the intestinal microbiota has gained increasing attention as a promising avenue for addressing mood disorders. This study aimed to assess the potential effect of supplementing standard pharmacological treatment with the probiotic kefir in patients with Major Depressive Disorder (MDD).</p><p><strong>Methods: </strong>Thirty-eight female participants diagnosed with moderate MDD by the Hamilton Rating Scale for Depression (HAM-D) were selected to receive the probiotic kefir in conjunction with antidepressant therapy for 12 weeks. The participants were evaluated at baseline (T0) and 90 days after probiotic kefir supplementation (T90). HAM-D scores and blood samples were collected at both time points.</p><p><strong>Results: </strong>Probiotic supplementation significantly reduced MDD severity, as evidenced by lower HAM-D scores compared to baseline. Probiotic consumption for 90 days also significantly decreased interleukin-6 (IL-6), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels compared to baseline. However, probiotic kefir supplementation did not significantly affect serum serotonin levels. Additionally, after 90 days of probiotic consumption, insulin and morning cortisol levels were significantly reduced. In contrast, no significant changes were observed in serum levels of prolactin, vitamin D, and afternoon cortisol.</p><p><strong>Conclusion: </strong>This study provides valuable insights into the potential benefits of probiotics, specifically kefir, as adjunctive therapy for female patients with MDD. The findings highlight promising results in ameliorating depressive symptoms and modulating inflammatory and hormonal markers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"463-473"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-01-20DOI: 10.1007/s43440-025-00694-w
Sajad Abolfazli, Sercan Karav, Thomas P Johnston, Amirhossein Sahebkar
{"title":"Regulatory effects of resveratrol on nitric oxide signaling in cardiovascular diseases.","authors":"Sajad Abolfazli, Sercan Karav, Thomas P Johnston, Amirhossein Sahebkar","doi":"10.1007/s43440-025-00694-w","DOIUrl":"10.1007/s43440-025-00694-w","url":null,"abstract":"<p><p>Cardiovascular illnesses are multifactorial disorders and represent the primary reasons for death worldwide, according to the World Health Organization. As a signaling molecule, nitric oxide (NO) is extremely permeable across cellular membranes owing to its unique molecular features, like its small molecular size, lipophilicity, and free radical properties. Some of the biological effects of NO are vasodilation, inhibition in the growth of vascular smooth muscle cells, and functional regulation of cardiac cells. Several therapeutic approaches have been tested to increase the production of NO or some downstream NO signaling pathways. The health benefits of red wine are typically attributed to the polyphenolic phytoalexin, resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is found in several plant species. Resveratrol has beneficial cardiovascular properties, some of which are mediated through endothelial nitric oxide synthase production (eNOS). Resveratrol promotes NO generation from eNOS through various methods, including upregulation of eNOS expression, activation in the enzymatic activity of eNOS, and reversal of eNOS uncoupling. Additionally, by reducing of oxidative stress, resveratrol inhibits the formation of superoxide and inactivation NO, increasing NO bioavailability. This review discusses the scientific literature on resveratrol's beneficial impact on NO signaling and how this effect improves the function of vascular endothelium.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"355-374"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-01-21DOI: 10.1007/s43440-024-00693-3
Minyan Qian, Mengmeng Guan, Liying Wang, Nan Hu
{"title":"Tacrolimus and diabetic rodent models.","authors":"Minyan Qian, Mengmeng Guan, Liying Wang, Nan Hu","doi":"10.1007/s43440-024-00693-3","DOIUrl":"10.1007/s43440-024-00693-3","url":null,"abstract":"<p><p>Tacrolimus (TAC) is an immunosuppressant widely utilized in organ transplantation. One of its primary adverse effects is glucose metabolism disorder, which significantly increases the risk of diabetes. Investigating the molecular mechanisms underlying TAC-induced diabetes is essential for developing effective prevention and treatment strategies for these adverse effects. In addition, TAC can induce cost-effective, non-obese animal models of diabetes, where the metabolic parameter changes closely resemble those observed during the onset and progression of type 2 diabetes (T2DM), post-transplantation diabetes mellitus (PTDM), and associated complications. This review, based on articles indexed in PubMed up to August 19, 2024, identified 48 studies focusing on TAC-induced diabetic rodent models and 22 studies exploring the effects of TAC on diabetic or obese rodent models. These studies were systematically summarized based on TAC dosage, route of administration, duration of administration, and glucose metabolism indices used for evaluation. Additionally, the impact of TAC dose reduction or discontinuation on glucose metabolism was assessed, along with pharmacological agents that modulate TAC-induced diabetes, including anti-diabetic medications, anti-inflammatory and antioxidant compounds, biologics, and antibiotics. Key signaling pathways implicated in TAC-induced diabetes include CaN/NFAT, PI3K/AKT/mTOR, and TGF-β/Smad, all of which impair islet β-cell function, thereby contributing to diabetes development. This review provides a concise summary of the characteristics of relevant murine models, offering valuable guidance for selecting appropriate and economical animal models for future research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"333-354"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2025-04-01Epub Date: 2025-02-03DOI: 10.1007/s43440-025-00696-8
Laura A Borba, Getúlio Antonio de Freitas Filho, Taiane de Azevedo Cardoso, Camila O Arent, Flávia S Niero, Lucas C Pedro, Caion A Rodrigues, Lara R Cichella, Margarete D Bagatini, Gabriela Gonçalves de Oliveira, Gilnei Bruno da Silva, Daiane Manica, Zuleide Maria Ignácio, João Quevedo, Luciane B Ceretta, Gislaine Z Réus
{"title":"Effects of COVID-19 and medication used for treatment and symptom prevention on the antioxidant status.","authors":"Laura A Borba, Getúlio Antonio de Freitas Filho, Taiane de Azevedo Cardoso, Camila O Arent, Flávia S Niero, Lucas C Pedro, Caion A Rodrigues, Lara R Cichella, Margarete D Bagatini, Gabriela Gonçalves de Oliveira, Gilnei Bruno da Silva, Daiane Manica, Zuleide Maria Ignácio, João Quevedo, Luciane B Ceretta, Gislaine Z Réus","doi":"10.1007/s43440-025-00696-8","DOIUrl":"10.1007/s43440-025-00696-8","url":null,"abstract":"<p><strong>Background: </strong>It is known that an inflammatory response plays a key role in COVID-19 pathogenesis. An exacerbated inflammatory response can increase oxidative stress in cells. This study aimed to investigate the effects of COVID-19 on parameters of oxidative stress including non-protein thiol antioxidants (NPSH), protein thiols (PSH), total antioxidant capacity (TAC), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), ascorbic acid, and reactive oxygen species (ROS) in plasma collected four to six weeks after the diagnosis.</p><p><strong>Methods: </strong>This cross-sectional study included a sex-matched sample of 296 adult individuals with 112 positives (cases) and 184 negatives (controls) for COVID-19. Oxidative stress parameters were peripherally analyzed according to previous methods.</p><p><strong>Results: </strong>The results showed a decrease in NPSH (p = 0.004), TAC (p = 0.005), ROS (p < 0.001), and ascorbic acid (p < 0.001) in cases. TBARS were higher in moderate and severe cases of COVID-19 compared to asymptomatic and mild cases (p = 0.049). AOPP, PSH, and MPO were not significantly different between cases and controls. In the total sample, individuals who self-reported using medication to prevent or treat COVID-19 showed decreased NPSH (p = 0.034), TAC (p = 0.020), ascorbic acid (p = 0.010), and ROS (p = 0.001) compared to those who self-reported not using medication to prevent or treat COVID-19.</p><p><strong>Conclusions: </strong>In conclusion, individuals with COVID-19 had decreased antioxidant status. Furthermore, disease severity was associated with more lipid damage. Antioxidant therapies may be essential to prevent the impacts of COVID-19.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"490-499"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of risedronate and its regioisomers synthesized via microwave-assisted method: bone affinity, cytotoxicity, permeability, and therapeutic potential.","authors":"Monika Zielińska, Amanda Pacholak, Bartosz Orwat, Mariusz Sandomierski, Ireneusz Kownacki, Ewa Kaczorek, Adam Voelkel","doi":"10.1007/s43440-025-00703-y","DOIUrl":"10.1007/s43440-025-00703-y","url":null,"abstract":"<p><strong>Background: </strong>Bisphosphonates (BPs) are widely used for treating bone diseases such as osteoporosis due to their strong affinity for hydroxyapatite (HA) in bones. Minor structural variations among BPs can significantly affect their therapeutic potential. This study aimed to synthesize risedronate (RSD) and its two regioisomers (2-RSD, 4-RSD) and investigate the impact of these variations on bone affinity, permeability, and cytotoxicity.</p><p><strong>Methods: </strong>RSD and its regioisomers were synthesized using a microwave-assisted method. Bone affinity was assessed through sorption studies on HA and two polymer-ceramic materials mimicking bone properties. Compound permeability was predicted using the Parallel Artificial Membrane Permeability Assay (PAMPA). Cytotoxicity was evaluated by analyzing the response of bacterial cells to BPs using metabolic activity assays.</p><p><strong>Results: </strong>2-RSD demonstrated a higher bone affinity and similar permeability than commercially available RSD. 2-RSD also showed reduced cytotoxicity in bacterial cell assays, indicating enhanced biocompatibility. These findings suggest that minor structural changes can lead to significant differences in therapeutic efficacy.</p><p><strong>Conclusions: </strong>The study highlights the potential of the 2-RSD as a more effective treatment for bone diseases. Structural variations in BPs can greatly influence their biological properties, paving the way for the development of improved therapeutic agents.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"517-531"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoyou Shi, Peyman Sahbaie, Tian-Zhi Guo, Yen-Ming Hsu, Wade S Kingery, J David Clark
{"title":"Blockade of IgG Fc receptors reduces pain after intervertebral disc injury.","authors":"Xiaoyou Shi, Peyman Sahbaie, Tian-Zhi Guo, Yen-Ming Hsu, Wade S Kingery, J David Clark","doi":"10.1007/s43440-025-00720-x","DOIUrl":"https://doi.org/10.1007/s43440-025-00720-x","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc (IVD) injury is a common cause of low back pain and disability. Recent evidence suggests that autoantibodies contribute to such pain. We, therefore, explored the hypothesis that a novel IgG Fc receptor blocker could reverse chronic pain-related behaviors in a mouse model of IVD injury.</p><p><strong>Methods: </strong>These studies used a multi-level lumbar IVD puncture model of low back pain in male C57BL/6 mice. Additional mouse strains evaluated included Fc gamma chain knockouts failing to express excitatory IgG Fc receptors and muMT mice incapable of producing mature B lymphocytes or antigen-specific IgG. Nociceptive testing consisted of hindpaw mechanical allodynia and pinch hyperalgesia. The expression of FcgrI and FcgrIII excitatory IgG Fc receptors and FcgrIIb inhibitory receptors was measured in lumbar sensory ganglia and spinal cord tissue using qPCR. The accumulation of IgG was measured using immunoblotting.</p><p><strong>Results: </strong>After disc injury, wild-type mice developed chronic hindpaw mechanical allodynia and pinch hyperalgesia. At 10 weeks post-injury, FcgrI, FcgrIIb and FcgrIII receptor expression were all increased in lumbar sensory ganglia and lumbar spinal cord tissue. Disc injury also caused IgG deposition at 10 weeks in the injured tissues and corresponding spinal cord. Treating disc-injured mice with the pan IgG Fc receptor interacting molecule (PRIM) reversed pain behaviors.</p><p><strong>Conclusions: </strong>Injury of mouse IVDs leads to persistent nociceptive sensitization in mice which can be reduced by administration of PRIM. Blockade of IgG Fc receptors may be a viable approach to the treatment of low back pain.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}