{"title":"Rat Sympathetic Neuron Calcium Channels Are Insensitive to Gabapentin.","authors":"Mallory B Scott, Paul J Kammermeier","doi":"10.3390/ph17091237","DOIUrl":null,"url":null,"abstract":"<p><p>The gabapentenoids such as gabapentin (GP) and pregabalin are approved for the treatment of chronic pain, but their utility is limited by persistent side effects. These adverse effects result from GPs affecting many types of neurons and muscle cells, not just the pain-sensing neurons that are the intended targets. We have recently discovered a type of peripheral neuron, rat sympathetic neurons from the superior cervical ganglion (SCG), that is uniquely insensitive to GP effects. Currents were measured using whole-cell patch-clamp electrophysiology from cells in primary culture from either the SCG or the Nodose Ganglion (NDG) as a positive control for the effects of GP. We find that the calcium current density was dramatically reduced by GP pretreatment in NDG neurons, but that neurons from the SCG were resistant. Further, when GP was cytoplasmically injected into these neurons, the resistance of SCG neurons to GP treatment persisted. These data demonstrate that rat sympathetic neurons appear to be uniquely resistant to GP treatment. These results may help us to better understand the mechanism of action of, and resistance to, GP in altering calcium channel current density, which may help to develop future treatments with fewer side effects.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11435301/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3390/ph17091237","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
The gabapentenoids such as gabapentin (GP) and pregabalin are approved for the treatment of chronic pain, but their utility is limited by persistent side effects. These adverse effects result from GPs affecting many types of neurons and muscle cells, not just the pain-sensing neurons that are the intended targets. We have recently discovered a type of peripheral neuron, rat sympathetic neurons from the superior cervical ganglion (SCG), that is uniquely insensitive to GP effects. Currents were measured using whole-cell patch-clamp electrophysiology from cells in primary culture from either the SCG or the Nodose Ganglion (NDG) as a positive control for the effects of GP. We find that the calcium current density was dramatically reduced by GP pretreatment in NDG neurons, but that neurons from the SCG were resistant. Further, when GP was cytoplasmically injected into these neurons, the resistance of SCG neurons to GP treatment persisted. These data demonstrate that rat sympathetic neurons appear to be uniquely resistant to GP treatment. These results may help us to better understand the mechanism of action of, and resistance to, GP in altering calcium channel current density, which may help to develop future treatments with fewer side effects.
加巴喷丁(GP)和普瑞巴林等加巴喷丁类药物已被批准用于治疗慢性疼痛,但它们的作用因持续的副作用而受到限制。这些不良反应是由于 GP 影响了多种类型的神经元和肌肉细胞,而不仅仅是作为预期目标的痛觉神经元。我们最近发现了一种外周神经元,即来自颈上神经节(SCG)的大鼠交感神经元,这种神经元对 GP 效应独特地不敏感。我们使用全细胞膜片钳电生理学方法测量了来自 SCG 或结节神经节(NDG)原代培养细胞的电流,作为 GP 影响的阳性对照。我们发现,在 NDG 神经元中,GP 预处理会显著降低钙电流密度,而 SCG 神经元则没有这种作用。此外,当将 GP 注入这些神经元的细胞质中时,SCG 神经元对 GP 处理的抗性依然存在。这些数据表明,大鼠交感神经元似乎对 GP 治疗具有独特的抵抗力。这些结果可能有助于我们更好地了解 GP 在改变钙通道电流密度方面的作用机制和抗药性,从而有助于开发副作用更小的未来治疗方法。