کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
914522 918401 2010 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Acetazolamide and midazolam act synergistically to inhibit neuropathic pain
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
Acetazolamide and midazolam act synergistically to inhibit neuropathic pain
چکیده انگلیسی
Treatment of neuropathic pain is a major clinical challenge that has been met with minimal success. After peripheral nerve injury, a decrease in the expression of the K-Cl cotransporter KCC2, a major neuronal Cl− extruder, leads to pathologic alterations in GABAA and glycine receptor function in the spinal cord. The down-regulation of KCC2 is expected to cause a reduction in Cl− extrusion capacity in dorsal horn neurons, which, together with the depolarizing efflux of HCO3- anions via GABAA channels, would result in a decrease in the efficacy of GABAA-mediated inhibition. Carbonic anhydrases (CA) facilitate intracellular HCO3- generation and hence, we hypothesized that inhibition of CAs would enhance the efficacy of GABAergic inhibition in the context of neuropathic pain. Despite the decrease in KCC2 expression, spinal administration of benzodiazepines has been shown to be anti-allodynic in neuropathic conditions. Thus, we also hypothesized that spinal inhibition of CAs might enhance the anti-allodynic effects of spinally administered benzodiazepines. Here, we show that inhibition of spinal CA activity with acetazolamide (ACT) reduces neuropathic allodynia. Moreover, we demonstrate that spinal co-administration of ACT and midazolam (MZL) act synergistically to reduce neuropathic allodynia after peripheral nerve injury. These findings indicate that the combined use of CA inhibitors and benzodiazepines may be effective in the clinical management of neuropathic pain in humans.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN - Volume 148, Issue 2, February 2010, Pages 302-308
نویسندگان
, , , ,