کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8517009 | 1556584 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Involvement of glycine receptor α1 subunits in cannabinoid-induced analgesia
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Some cannabinoids have been shown to suppress chronic pain by targeting glycine receptors (GlyRs). Although cannabinoid potentiation of α3 GlyRs is thought to contribute to cannabinoid-induced analgesia, the role of cannabinoid potentiation of α1 GlyRs in cannabinoid suppression of chronic pain remains unclear. Here we report that dehydroxylcannabidiol (DH-CBD), a nonpsychoactive cannabinoid, significantly suppresses chronic inflammatory pain caused by noxious heat stimulation. This effect may involve spinal α1 GlyRs since the expression level of α1 subunits in the spinal cord is positively correlated with CFA-induced inflammatory pain and the GlyRs antagonist strychnine blocks the DH-CBD-induced analgesia. A point-mutation of S296A in TM3 of α1 GlyRs significantly inhibits DH-CBD potentiation of glycine currents (IGly) in HEK-293â¯cells and neurons in lamina I-II of spinal cord slices. To explore the in vivo consequence of DH-CBD potentiation of α1 GlyRs, we generated a GlyRα1S296A knock-in mouse line. We observed that DH-CBD-induced potentiation of IGly and analgesia for inflammatory pain was absent in GlyRα1S296A knock-in mice. These findings suggest that spinal α1 GlyR is a potential target for cannabinoid analgesia in chronic inflammatory pain.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 133, 1 May 2018, Pages 224-232
Journal: Neuropharmacology - Volume 133, 1 May 2018, Pages 224-232
نویسندگان
Jieping Lu, Sijia Fan, Guichang Zou, Yiwen Hou, Tao Pan, Weiwei Guo, Lei Yao, Feng Du, Gregg E. Homanics, Dan Liu, Li Zhang, Wei Xiong,