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Epiregulin and EGFR interactions are involved in pain processing.

Publication ,  Journal Article
Martin, LJ; Smith, SB; Khoutorsky, A; Magnussen, CA; Samoshkin, A; Sorge, RE; Cho, C; Yosefpour, N; Sivaselvachandran, S; Tohyama, S; Cole, T ...
Published in: J Clin Invest
September 1, 2017

The EGFR belongs to the well-studied ErbB family of receptor tyrosine kinases. EGFR is activated by numerous endogenous ligands that promote cellular growth, proliferation, and tissue regeneration. In the present study, we have demonstrated a role for EGFR and its natural ligand, epiregulin (EREG), in pain processing. We show that inhibition of EGFR with clinically available compounds strongly reduced nocifensive behavior in mouse models of inflammatory and chronic pain. EREG-mediated activation of EGFR enhanced nociception through a mechanism involving the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9. Moreover, EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons. Both the EGFR and EREG genes displayed a genetic association with the development of chronic pain in several clinical cohorts of temporomandibular disorder. Thus, EGFR and EREG may be suitable therapeutic targets for persistent pain conditions.

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

September 1, 2017

Volume

127

Issue

9

Start / End Page

3353 / 3366

Location

United States

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Protein Binding
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Pain Management
  • Neurons
  • Mutation
  • Mice
  • Matrix Metalloproteinase 9
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Martin, L. J., Smith, S. B., Khoutorsky, A., Magnussen, C. A., Samoshkin, A., Sorge, R. E., … Diatchenko, L. (2017). Epiregulin and EGFR interactions are involved in pain processing. J Clin Invest, 127(9), 3353–3366. https://doi.org/10.1172/JCI87406
Martin, Loren J., Shad B. Smith, Arkady Khoutorsky, Claire A. Magnussen, Alexander Samoshkin, Robert E. Sorge, Chulmin Cho, et al. “Epiregulin and EGFR interactions are involved in pain processing.J Clin Invest 127, no. 9 (September 1, 2017): 3353–66. https://doi.org/10.1172/JCI87406.
Martin LJ, Smith SB, Khoutorsky A, Magnussen CA, Samoshkin A, Sorge RE, et al. Epiregulin and EGFR interactions are involved in pain processing. J Clin Invest. 2017 Sep 1;127(9):3353–66.
Martin, Loren J., et al. “Epiregulin and EGFR interactions are involved in pain processing.J Clin Invest, vol. 127, no. 9, Sept. 2017, pp. 3353–66. Pubmed, doi:10.1172/JCI87406.
Martin LJ, Smith SB, Khoutorsky A, Magnussen CA, Samoshkin A, Sorge RE, Cho C, Yosefpour N, Sivaselvachandran S, Tohyama S, Cole T, Khuong TM, Mir E, Gibson DG, Wieskopf JS, Sotocinal SG, Austin JS, Meloto CB, Gitt JH, Gkogkas C, Sonenberg N, Greenspan JD, Fillingim RB, Ohrbach R, Slade GD, Knott C, Dubner R, Nackley AG, Ribeiro-da-Silva A, Neely GG, Maixner W, Zaykin DV, Mogil JS, Diatchenko L. Epiregulin and EGFR interactions are involved in pain processing. J Clin Invest. 2017 Sep 1;127(9):3353–3366.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

September 1, 2017

Volume

127

Issue

9

Start / End Page

3353 / 3366

Location

United States

Related Subject Headings

  • Young Adult
  • Signal Transduction
  • Protein Binding
  • Polymorphism, Single Nucleotide
  • Phosphorylation
  • Pain Management
  • Neurons
  • Mutation
  • Mice
  • Matrix Metalloproteinase 9