کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
7270624 1473239 2009 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب سلولی و مولکولی
پیش نمایش صفحه اول مقاله
The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome
چکیده انگلیسی
Tibia fracture followed by limb immobilization in rats evokes nociceptive and vascular changes resembling complex regional pain syndrome type I (CRPS I). Previously we observed that substance P (SP) and interleukin-1β (IL-1β) signaling contribute to chronic regional nociceptive sensitization in this model. It is known that inflammasome multi-protein complexes containing caspase-1 and NALP1 are involved in the activation of the IL-1β family of pro-nociceptive cytokines expressed in skin and other tissues. Therefore, we hypothesized that SP activated inflammasomes might contribute to mechanical allodynia after fracture. Using this model we observed that: (1) inflammasome components and products NALP1, caspase-1, IL-1β and IL-18 were present in low levels in normal skin, but expression of all these was strongly up-regulated after fracture, (2) NALP1, caspase-1 and IL-1β were co-expressed in keratinocytes, and the number of NALP1, caspase-1, and IL-1β positive cells dramatically increased at 4 weeks post-fracture, (3) LY303870, an NK1 receptor antagonist, effectively blocked fracture-induced up-regulation of activated inflammasome components and cytokines, (4) IL-1β and IL-18 intraplantar injection induced mechanical allodynia in normal rats, and (5) both a selective caspase-1 inhibitor and an IL-1 receptor antagonist attenuated fracture-induced hindpaw mechanical allodynia. Collectively, these data suggest that NALP1 containing inflammasomes activated by NK1 receptors are expressed in keratinocytes and contribute to post-traumatic regional nociceptive sensitization. These findings highlight the possible importance of neuro-cutaneous signaling and innate immunity mechanisms in the development of CRPS.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: PAIN® - Volume 147, Issues 1–3, 15 December 2009, Pages 277-286
نویسندگان
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