In vivo luminescent imaging of NF-κB activity and NF-κB-related serum cytokine levels predict pain sensitivities in a rodent model of peripheral neuropathy.
In vivo luminescent imaging of NF-κB activity and NF-κB-related serum cytokine levels predict pain sensitivities in a rodent model of peripheral neuropathy.
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DOI：
10.1002/ejp.732
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发表时间：
2016-03
期刊：
影响因子：
--
通讯作者：
Setton LA
中科院分区：
文献类型：
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作者：
Bowles RD;Karikari IO;VanDerwerken DN;Sinclair MS;Bell RD;Riebe KJ;Huebner JL;Kraus VB;Sempowski GD;Setton LA
需要用于检测疼痛症状的时间和空间产生的方法来改善疼痛性神经病的诊断和治疗，并帮助分子治疗的临床前筛选。在这项研究中，我们利用NF-κB活性的体内发光成像和血清细胞因子测量来研究NF-κB调节网络与神经病模型中疼痛症状的表现之间的关系。慢性压迫性损伤模型导致NF-κB活性暂时增加，这与疼痛敏感性（即机械异常性疼痛和热痛觉过敏）的表现强烈且非线性相关。NEMO结合域肽的递送通过以与所证明的非线性关系一致的方式抑制NF-κB活性来降低疼痛敏感性。重要的是，NF-κB活性的非侵入性测量和NF-κB调节的血清细胞因子的组合产生了以NF-κB调节网络（NF-κB、IL-6、CXCL 1）为中心的机械（R2=0.86）和热（R2=0.76）疼痛的高度预测模型。利用NF-κB活性的体内发光成像和血清细胞因子的测量，这项工作建立了NF-κB和NF-κB调节的细胞因子作为这种神经病模型中疼痛相关敏感性的新的多变量生物标志物，这可能有助于快速筛选新的分子疗法。
Methods for the detection of the temporal and spatial generation of painful symptoms are needed to improve the diagnosis and treatment of painful neuropathies and to aid preclinical screening of molecular therapeutics. In this study, we utilized in vivo luminescent imaging of NF-κB activity and serum cytokine measures to investigate relationships between the NF-κB regulatory network and the presentation of painful symptoms in a model of neuropathy. The chronic constriction injury model led to temporal increases in NF-κB activity that were strongly and non-linearly correlated with the presentation of pain sensitivities (i.e. mechanical allodynia and thermal hyperalgesia). The delivery of NEMO-binding domain peptide reduced pain sensitivities through the inhibition of NF-κB activity in a manner consistent with the demonstrated non-linear relationship. Importantly, the combination of non-invasive measures of NF-κB activity and NF-κB regulated serum cytokines produced a highly predictive model of both mechanical (R2=0.86) and thermal (R2=0.76) pain centered on the NF-κB regulatory network (NF-κB, IL-6, CXCL1). Using in vivo luminescent imaging of NF-κB activity and serum cytokine measures, this work establishes NF-κB and NF-κB regulated cytokines as novel multivariate biomarkers of pain-related sensitivity in this model of neuropathy that may be useful for the rapid screening of novel molecular therapeutics.