کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8840604 | 1614691 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Spinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Spinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice Spinal Inhibition of P2XR or p38 Signaling Disrupts Hyperalgesic Priming in Male, but not Female, Mice](/preview/png/8840604.png)
چکیده انگلیسی
Recent studies have demonstrated sexual dimorphisms in the mechanisms contributing to the development of chronic pain. Here we tested the hypothesis that microglia might preferentially regulate hyperalgesic priming in male mice. We based this hypothesis on evidence that microglia preferentially contribute to neuropathic pain in male mice via ionotropic purinergic receptor (P2XR) or p38 mitogen-activated protein kinase (p38) signaling. Mice given a single-priming injection of the soluble human interleukin-6 receptor (IL-6r) and then a second injection of prostaglandin E2 (PGE2), which unmasks hyperalgesic priming, shows a significant increase in levels of activated microglia at 3â¯h following the PGE2 injection in both male and female mice. There was no change in microglia following PGE2. Intrathecal injection of the P2X3/4 inhibitor TNP-ATP blocked the initial response to IL-6r in both males and females, but only blocked hyperalgesic priming in male mice. Intrathecally applied p38 inhibitor, skepinone, had no effect on the initial response to IL-6r but attenuated hyperalgesic priming in males only. Neither TNP-ATP nor skepinone could reverse priming once it had already been established in male mice suggesting that these pathways must be inhibited early in the development of hyperalgesic priming to have an effect. Our work is consistent with previous findings that P2XR and p38 inhibition can lead to male-specific effects on pain behaviors in mice. However, given that we did not observe microglial activation at time points where these drugs were effective, our work also questions whether these effects can be completely attributed to microglia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 385, 10 August 2018, Pages 133-142
Journal: Neuroscience - Volume 385, 10 August 2018, Pages 133-142
نویسندگان
Candler Paige, Gayathri Batchalli Maruthy, Galo Mejia, Gregory Dussor, Theodore Price,