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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.

Publication ,  Journal Article
Bowles, RD; Karikari, IO; VanDerwerken, DN; Sinclair, MS; Bell, RD; Riebe, KJ; Huebner, JL; Kraus, VB; Sempowski, GD; Setton, LA
Published in: Eur J Pain
March 2016

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.

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Published In

Eur J Pain

DOI

EISSN

1532-2149

Publication Date

March 2016

Volume

20

Issue

3

Start / End Page

365 / 376

Location

England

Related Subject Headings

  • Physical Stimulation
  • Peripheral Nervous System Diseases
  • Peptides
  • Pain Threshold
  • Pain
  • NF-kappa B
  • Mice, Inbred BALB C
  • Mice
  • Metabolic Networks and Pathways
  • Male
 

Citation

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Bowles, R. D., Karikari, I. O., VanDerwerken, D. N., Sinclair, M. S., Bell, R. D., Riebe, K. J., … Setton, L. A. (2016). 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. Eur J Pain, 20(3), 365–376. https://doi.org/10.1002/ejp.732
Bowles, R. D., I. O. Karikari, D. N. VanDerwerken, M. S. Sinclair, R. D. Bell, K. J. Riebe, J. L. Huebner, V. B. Kraus, G. D. Sempowski, and L. A. Setton. “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.Eur J Pain 20, no. 3 (March 2016): 365–76. https://doi.org/10.1002/ejp.732.
Bowles RD, Karikari IO, VanDerwerken DN, Sinclair MS, Bell RD, Riebe KJ, et al. 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. Eur J Pain. 2016 Mar;20(3):365–76.
Bowles, R. D., et al. “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.Eur J Pain, vol. 20, no. 3, Mar. 2016, pp. 365–76. Pubmed, doi:10.1002/ejp.732.
Bowles RD, Karikari IO, VanDerwerken DN, Sinclair MS, Bell RD, Riebe KJ, Huebner JL, Kraus VB, Sempowski GD, Setton LA. 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. Eur J Pain. 2016 Mar;20(3):365–376.

Published In

Eur J Pain

DOI

EISSN

1532-2149

Publication Date

March 2016

Volume

20

Issue

3

Start / End Page

365 / 376

Location

England

Related Subject Headings

  • Physical Stimulation
  • Peripheral Nervous System Diseases
  • Peptides
  • Pain Threshold
  • Pain
  • NF-kappa B
  • Mice, Inbred BALB C
  • Mice
  • Metabolic Networks and Pathways
  • Male