کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10450223 | 918349 | 2014 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inflammatory and neuropathic pain are rapidly suppressed by peripheral block of hyperpolarisation-activated cyclic nucleotide-gated ion channels
ترجمه فارسی عنوان
درد های التهابی و نوروپاتیک به سرعت توسط بلوک محیطی از کانال های یونی نوکلئوتید سیکل فعال
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
چکیده انگلیسی
Previous studies have shown that hyperpolarisation-activated cyclic nucleotide-gated (HCN)-2 ion channels regulate the firing frequency of nociceptive sensory neurons and thus play a central role in both inflammatory and neuropathic pain conditions. Here we use ivabradine, a clinically approved anti-anginal agent that blocks all HCN channel isoforms approximately equally, to investigate the effect on inflammatory and neuropathic pain of HCN ion channel block. We show that ivabradine does not have major off-target effects on a sample group of Na, Ca, and K ion channels, and that it is peripherally restricted because it is a substrate for the P-glycoprotein (PgP) multidrug transporter that is expressed in the blood-brain barrier. Its effects are therefore likely to be due to an action on HCN ion channels in peripheral sensory neurons. Using patch clamp electrophysiology, we found that ivabradine was a use-dependent blocker of native HCN channels expressed in small sensory neurons. Ivabradine suppressed the action potential firing that is induced in nociceptive neurons by elevation of intracellular cAMP. In the formalin model of inflammatory pain, ivabradine reduced pain behaviour only in the second (inflammatory) phase. In nerve injury and chemotherapy models of neuropathic pain, we observed rapid and effective analgesia as effective as that with gabapentin. We conclude that both inflammatory and neuropathic pain are rapidly inhibited by blocking HCN-dependent repetitive firing in peripheral nociceptive neurons.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN® - Volume 155, Issue 9, September 2014, Pages 1708-1719
Journal: PAIN® - Volume 155, Issue 9, September 2014, Pages 1708-1719
نویسندگان
Gareth T. Young, Edward C. Emery, Elizabeth R. Mooney, Christoforos Tsantoulas, Peter A. McNaughton,