Diabetic neuropathic pain: a role for testosterone metabolites
Diabetic neuropathic pain: a role for testosterone metabolites
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DOI：
10.1530/joe-13-0541
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发表时间：
2014-04-01
影响因子：
4
通讯作者：
Melcangi, Roberto Cosimo
中科院分区：
文献类型：
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作者：
Calabrese, Donato;Giatti, Silvia;Melcangi, Roberto Cosimo
在约50%的糖尿病受试者中，糖尿病神经病变与神经性疼痛相关。神经病理性疼痛的临床管理是复杂的，迄今为止并不令人满意。在这项研究中，我们分析了睾酮代谢产物，双氢睾酮（DHT），和3 α-二醇，伤害性和异常性疼痛阈值和分子和功能参数相关的疼痛调制在脊髓背角和糖尿病大鼠的背根神经节注射链脲佐菌素的影响。此外，在脊髓中分析了DHT和3 α-二醇的水平。糖尿病导致脊髓中的DHT水平显著降低，通过DHT或3 α-二醇治疗恢复。此外，与对照值相比，3 α-二醇处理导致脊髓中3 α-二醇显著增加。这两种类固醇对糖尿病神经性疼痛表现出镇痛特性，影响不同的疼痛参数，并可能通过不同的作用机制。事实上，DHT抵消了糖尿病对机械伤害性阈值、突触前和突触后成分、谷氨酸释放、星形胶质细胞免疫反应性和白细胞介素-1 β表达的影响（IL 1 β），而3 α-二醇对触觉异常性疼痛阈值、谷氨酸释放、星形胶质细胞免疫反应性以及P物质、Toll样受体4、肿瘤坏死因子-α的表达有效，转化生长因子β 1、IL 1 β和转运蛋白。这些结果表明，睾酮代谢产物是治疗糖尿病神经病理性疼痛的潜在药物。
Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3 alpha-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3 alpha-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3 alpha-diol treatments. In addition, 3 alpha-diol treatment resulted in a significant increase in 3 alpha-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre- and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1 beta (IL1 beta), while 3 alpha-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-alpha, transforming growth factor beta-1, IL1 beta, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain.