کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6282506 1615141 2014 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Presynaptic inhibitory actions of pregabalin on excitatory transmission in superficial dorsal horn of mouse spinal cord: Further characterization of presynaptic mechanisms
ترجمه فارسی عنوان
اقدامات مهارکننده پیشینپتیک پیشگابالین در انتقال هیجان انگیز در شاخ پشتی نخاعی موش صحرایی: مشخصه بیشتر مکانیسمهای پیشینپتیک
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- Antisense ODN reduced Ca channel α2δ-1 expression and weakened pregabalin's action.
- Nerve injury increased Ca channel α2δ-1 expression and augmented pregabalin's action.
- Pregabalin's presynaptic actions were attenuated in syntaxin 1A knockout mice.
- Syntaxin 1A is necessary for pregabalin to exert its full presynaptic inhibition.

Pregabalin is widely used as an analgesic for the treatment of neuropathic pain. In the present experiments using mouse spinal slices, we recorded electrically evoked glutamatergic excitatory postsynaptic currents (eEPSCs) from superficial dorsal horn neurons. Pregabalin reduced the amplitude of eEPSCs, and increased the paired pulse ratio. Pregabalin also inhibited the frequency of spontaneously occurring miniature EPSCs without affecting their amplitude. Partial ligation of the sciatic nerve increased the expression of the calcium channel α2δ-1 subunit, and increased the presynaptic inhibitory action of pregabalin. Intrathecal injection of antisense oligodeoxynucleotide against the α2δ-1 subunit, decreased the expression of α2δ-1 mRNA in the spinal dorsal horn, and decreased pregabalin's action. These results provide further evidence that pregabalin exerts its presynaptic inhibitory action via binding with the α2δ subunit in a state-dependent manner. Furthermore, presynaptic actions of pregabalin were attenuated in knockout mice lacking the protein syntaxin 1A, a component of the synaptic vesicle release machinery, indicating that syntaxin 1A is required for pregabalin to exert its full presynaptic inhibitory action. These observations might suggest that direct and/or indirect interactions with the presynaptic proteins composing the release machinery underlie at least some part of pregabalin's presynaptic actions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 558, 13 January 2014, Pages 186-191
نویسندگان
, , , , , , ,