{"title":"Calcium Channel α<sub>2</sub>δ Ligands Mirogabalin, Pregabalin, and Gabapentin: Advancements in Diabetic Peripheral Neuropathic Pain Therapeutics.","authors":"Yiming Wu, Xiaohui Guo, Junqing Zhang","doi":"10.1007/s40122-025-00771-1","DOIUrl":null,"url":null,"abstract":"<p><p>Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). α<sub>2</sub>δ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the α<sub>2</sub>δ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of the clinical trials have demonstrated the efficacy of α<sub>2</sub>δ ligands in providing pain relief and improvement in the QoL for patients with DPNP. Furthermore, α<sub>2</sub>δ ligands have a tolerable safety profile, with somnolence and dizziness being the most frequently reported adverse events. Currently, most guidelines recommend calcium channel α<sub>2</sub>δ ligands as first-line treatment for DPNP. With the development of drug research, mirogabalin, an emerging novel α<sub>2</sub>δ ligand, was developed and validated. This review aims to summarize the latest status of α<sub>2</sub>δ ligand development and provide a comprehensive evaluation of α<sub>2</sub>δ ligands for the management of DPNP, emphasizing the potential mechanism of action, clinical efficacy, safety profile, and pharmacoeconomics. Further perspectives are warranted for treatment strategies to address individual patient care.A Graphical Abstract is availible for this article.</p>","PeriodicalId":19908,"journal":{"name":"Pain and Therapy","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pain and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40122-025-00771-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Diabetic peripheral neuropathic pain (DPNP) is becoming increasingly prevalent as the global burden of diabetes continues to rise. DPNP manifests moderate-to-severe pain with burning, shooting, and tingling sensations, which increase clinical and economic burden and reduce the quality of life (QoL). α2δ ligands were developed on the basis of their mechanism of action involving the modulation of voltage-gated calcium channels (VGCCs). These ligands bind to the α2δ subunit of VGCCs, which reduces calcium influx and subsequently decreases the release of excitatory neurotransmitters. A majority of the clinical trials have demonstrated the efficacy of α2δ ligands in providing pain relief and improvement in the QoL for patients with DPNP. Furthermore, α2δ ligands have a tolerable safety profile, with somnolence and dizziness being the most frequently reported adverse events. Currently, most guidelines recommend calcium channel α2δ ligands as first-line treatment for DPNP. With the development of drug research, mirogabalin, an emerging novel α2δ ligand, was developed and validated. This review aims to summarize the latest status of α2δ ligand development and provide a comprehensive evaluation of α2δ ligands for the management of DPNP, emphasizing the potential mechanism of action, clinical efficacy, safety profile, and pharmacoeconomics. Further perspectives are warranted for treatment strategies to address individual patient care.A Graphical Abstract is availible for this article.
期刊介绍：
Pain and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of pain therapies and pain-related devices. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, acute pain, cancer pain, chronic pain, headache and migraine, neuropathic pain, opioids, palliative care and pain ethics, peri- and post-operative pain as well as rheumatic pain and fibromyalgia.
The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports, trial protocols, short communications such as commentaries and editorials, and letters. The journal is read by a global audience and receives submissions from around the world. Pain and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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