کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
914187 | 918385 | 2011 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Spinal TLR4 mediates the transition to a persistent mechanical hypersensitivity after the resolution of inflammation in serum-transferred arthritis
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
Persistent pain after resolution of clinically appreciable signs of arthritis poses a therapeutic challenge, and immunosuppressive therapies do not meet this medical need. To investigate this conversion to persistent pain, we utilized the K/BxN serum transfer arthritis model, which has persistent mechanical hypersensitivity despite the resolution of visible inflammation. Toll-like receptor (TLR) 4 has been implicated as a potential therapeutic target in neuropathic and other pain models. We compared the relative courses of serum transfer arthritis and mechanical hypersensitivity in wild type (WT) and Tlr4â/â mice. K/BxN serum transfer induced similar joint swelling and inflammation from days 4-22 in WT and Tlr4â/â mice. Unlike WT mice, Tlr4â/â mice displayed a significant reversal in mechanical hypersensitivity and diminished appearance of glial activation markers after resolution of peripheral inflammation. Intrathecal (IT) delivery of a TLR4 antagonist, lipopolysaccharide Rhodobacter sphaeroides (LPS-RS; 10 μg), on days 6, 9, and 12 abrogated the transition to persistent mechanical hypersensitivity in WT arthritic mice, while later administration had no impact. We utilized a lipidomics liquid chromatography tandem mass spectrometry methodology to determine spinal cord profiles of bioactive lipid species after early LPS-RS treatment compared to vehicle-treated control animals. WT arthritic mice had reduced spinal levels of the anti-inflammatory prostaglandin 15-deoxy-Î12,14-PGJ2 (15d-PGJ2) on day 6, compared to IT LPS-RS-treated mice. Direct IT application of 15d-PGJ2 (0.5 μg) on day 6 improved mechanical hypersensitivity in arthritic mice within 15 min. Hence, TLR4 signaling altered spinal bioactive lipid profiles in the serum transfer model and played a critical role in the transition from acute to chronic postinflammatory mechanical hypersensitivity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN - Volume 152, Issue 12, December 2011, Pages 2881-2891
Journal: PAIN - Volume 152, Issue 12, December 2011, Pages 2881-2891
نویسندگان
Christina A. Christianson, Darren S. Dumlao, Jennifer A. Stokes, Edward A. Dennis, Camilla I. Svensson, Maripat Corr, Tony L. Yaksh,