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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
Author(s) -
Bowles R.D.,
Karikari I.O.,
VanDerwerken D.N.,
Sinclair M.S.,
Bell R.D.,
Riebe K.J.,
Huebner J.L.,
Kraus V.B.,
Sempowski G.D.,
Setton L.A.
Publication year - 2016
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.732
Subject(s) - in vivo , neuropathic pain , cytokine , medicine , allodynia , nf κb , cxcl1 , peripheral neuropathy , inflammation , hyperalgesia , pharmacology , immunology , receptor , chemokine , endocrinology , biology , nociception , microbiology and biotechnology , diabetes mellitus
Background 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. Methods 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. Results 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 ( R 2 = 0.86) and thermal ( R 2 = 0.76) pain centred on the NF‐κB regulatory network (NF‐κB, IL‐6, CXCL1). Conclusions 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.