Scott Mallory B, Kammermeier Paul J
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Pharmaceuticals (Basel). 2024 Sep 19;17(9):1237. doi: 10.3390/ph17091237.
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.
加巴喷丁类药物，如加巴喷丁（GP）和普瑞巴林，已被批准用于治疗慢性疼痛，但其效用因持续的副作用而受到限制。这些不良反应是由于加巴喷丁类药物不仅影响预期目标的痛觉神经元，还影响多种类型的神经元和肌肉细胞。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，它对加巴喷丁类药物的作用具有独特的不敏感性。使用全细胞膜片钳电生理学方法，从原代培养的颈上神经节（SCG）或结状神经节（NDG）细胞中测量电流，将NDG细胞作为加巴喷丁类药物作用的阳性对照。我们发现，加巴喷丁预处理可显著降低NDG神经元中的钙电流密度，但SCG神经元具有抗性。此外，当将加巴喷丁注入这些神经元的细胞质中时，SCG神经元对加巴喷丁治疗的抗性仍然存在。这些数据表明，大鼠交感神经元似乎对加巴喷丁治疗具有独特的抗性。这些结果可能有助于我们更好地理解加巴喷丁在改变钙通道电流密度方面的作用机制和抗性，这可能有助于开发未来副作用更少的治疗方法。
