The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome.
The NALP1 inflammasome controls cytokine production and nociception in a rat fracture model of complex regional pain syndrome.
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DOI：
10.1016/j.pain.2009.09.032
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发表时间：
2009-12-15
期刊：
影响因子：
7.4
通讯作者：
Clark JD
中科院分区：
文献类型：
--
作者：
Li WW;Guo TZ;Liang D;Shi X;Wei T;Kingery WS;Clark JD
大鼠胫骨骨折后肢体固定引起类似于I型复杂区域疼痛综合征（CRPS I）的伤害性和血管变化。在此之前，我们观察到P物质（SP）和白细胞介素-1β (IL-1β)信号在该模型中参与慢性区域伤害性致敏。已知含有caspase-1和NALP1的炎性体多蛋白复合物参与皮肤和其他组织中表达的促伤害细胞因子IL-1β家族的激活。因此，我们假设SP激活的炎性小体可能有助于骨折后的机械异常性疼痛。使用这个模型，我们观察到：1)炎性小体成分和产物NALP1、caspase-1、IL-1β和IL-18在正常皮肤中表达水平较低，骨折后表达水平均显著上调；2)NALP1、caspase-1和IL-1β在角质形成细胞中共表达，骨折后4周NALP1、caspase-1和IL-1β阳性细胞数量显著增加；4) IL-1β和IL-18足底注射诱导正常大鼠机械性异位痛，5)选择性caspase-1抑制剂和IL-1受体拮抗剂均可减弱骨折诱导的后爪机械性异位痛。总的来说，这些数据表明含有NK1受体激活的炎性小体的NALP1在角化细胞中表达，并有助于创伤后区域伤害性致敏。这些发现强调了神经皮肤信号和先天免疫机制在CRPS发展中的可能重要性。
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 multiprotein 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 hind paw 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.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
158.5
作者：
Jin, Ying;Mailloux, Christina M.;Spritz, Richard A.
通讯作者：
Spritz, Richard A.
影响因子：
2.9
作者：
Dallos, Attila;Kiss, Maria;Husz, Sandor
通讯作者：
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影响因子：
4.6
作者：
Huygen, FJPM;de Bruijn, AGJ;Zijlstra, FJ
通讯作者：
Zijlstra, FJ
影响因子：
7.4
作者：
Kingery, WS;Davies, MF;Clark, JD
通讯作者：
Clark, JD