Alpha2delta-1 splice variants in neuropathic pain

在患者中，周围神经的损伤由许多不同的疾病引起，并且可能导致慢性疼痛，大多数常用的止痛药治疗效果不佳。常见的疾病，如糖尿病和疱疹感染，以及某些形式的化疗治疗，都可能导致神经损伤，这可能是不可逆的。一种名为加巴喷丁的药物（最初是为治疗癫痫而开发的）可以有效缓解这种类型的疼痛（称为神经性疼痛）。然而，加巴喷丁并不是对所有神经损伤疼痛患者都同样有效。我们知道加巴喷丁是如何治疗神经性疼痛的，因为它与一种叫做α 2 δ-1的蛋白质结合，在神经性疼痛的实验模型中，这种蛋白质在疼痛感受神经中的数量增加了几倍。我们的研究旨在检查是否在神经性疼痛条件下产生不同形式的alpha 2delta-1。这些形式可能显示出改变的特性，例如识别加巴喷丁的能力更高或更低。我们还将研究α 2 δ-1基因的遗传变异是否会影响加巴喷丁的敏感性。如果是这样的话，它可能与患者神经性疼痛的发展和治疗高度相关，因为它可能解释为什么加巴喷丁对所有患者都没有类似的效果。这项研究也有可能有助于开发这类新药，这些新药可能对某些患者或某些情况更有效。

In patients, damage to peripheral nerves results from many different diseases, and can result in chronic pain that is poorly treated by most of the commonly used pain killers. Common conditions such as diabetes and herpes infection, as well as treatment with certain forms of chemotherapy, can all cause nerve damage, which may be irreversible. A drug called gabapentin (initially developed for the treatment of epilepsy) is effective in the alleviation of this type of pain (which is called neuropathic pain). However, gabapentin is not equally effective in all patients with nerve-injury pain. We know how gabapentin works in the treatment of neuropathic pain, as it binds to a protein called alpha2delta-1, and the amount of this protein in pain-sensing nerves is increased several-fold in experimental models of neuropathic pain. Our study aims to examine whether different forms of alpha2delta-1 are produced in neuropathic pain conditions. These forms might show altered properties, such as higher or lower ability to recognise gabapentin. We will also investigate whether genetic variability in the gene for alpha2delta-1 may affect sensitivity to gabapentin. If this were the case it might be highly relevant to the development and treatment of neuropathic pain in patients, as it might explain why gabapentin is not similarly effective in all patients. It is also possible that this research will aid in the development of novel drugs in this class, that might have the potential to be more effective in certain patients or in certain conditions.