title: 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.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Bowles
authors.affiliation: Department of Neurosurgery, Duke University Medical Center, Durham, USA.
authors.forename: I O
authors.initials: IO
authors.lastname: Karikari
authors.affiliation: Department of Statistical Science, Duke University, Durham, USA.
authors.forename: D N
authors.initials: DN
authors.lastname: VanDerwerken
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Sinclair
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Bell
authors.affiliation: Department of Medicine and Human Vaccine Institute, Duke University, Durham, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Riebe
authors.affiliation: Department of Medicine, Division of Rheumatology and the Duke Molecular Physiology Institute, Durham, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Huebner
authors.affiliation: Department of Medicine, Division of Rheumatology and the Duke Molecular Physiology Institute, Durham, USA.
authors.forename: V B
authors.initials: VB
authors.lastname: Kraus
authors.affiliation: Department of Medicine and Human Vaccine Institute, Duke University, Durham, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Sempowski
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Setton
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D054360:Chemokine CXCL1 / Q000378:metabolism; D003251:Constriction, Pathologic / Q000150:complications / Q000473:pathology; D016207:Cytokines / Q000097:blood*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000523:psychology; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000523:psychology*; D017288:Pain Threshold; D010455:Peptides / Q000494:pharmacology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000523:psychology*; D010812:Physical Stimulation
chemical_list: D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D015850:Interleukin-6; C467063:NBD peptide, mouse; D016328:NF-kappa B; D010455:Peptides; C577686:interleukin-6, mouse