Display options
Cite
Berkey SC, Herrera JJ, Odem MA, et al. EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury. Neurobiol Pain. 2019;7:100040doi: 10.1016/j.ynpai.2019.100040.
Berkey, S. C., Herrera, J. J., Odem, M. A., Rahman, S., Cheruvu, S. S., Cheng, X., Walters, E. T., Dessauer, C. W., & Bavencoffe, A. G. (2020). EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury. Neurobiology of pain (Cambridge, Mass.), 7100040. https://doi.org/10.1016/j.ynpai.2019.100040
Berkey, Samantha C, et al. "EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury." Neurobiology of pain (Cambridge, Mass.) vol. 7 (2020): 100040. doi: https://doi.org/10.1016/j.ynpai.2019.100040
Berkey SC, Herrera JJ, Odem MA, Rahman S, Cheruvu SS, Cheng X, Walters ET, Dessauer CW, Bavencoffe AG. EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury. Neurobiol Pain. 2019 Dec 04;7:100040. doi: 10.1016/j.ynpai.2019.100040. eCollection 2020. PMID: 31890991; PMCID: PMC6926371.
Copy Download .nbib Format: NLM
Share it on

Neurobiol Pain. 2019 Dec 04;7:100040. doi: 10.1016/j.ynpai.2019.100040. eCollection 2020.

EPAC1 and EPAC2 promote nociceptor hyperactivity associated with chronic pain after spinal cord injury.

Neurobiology of pain (Cambridge, Mass.)

Samantha C Berkey, Juan J Herrera, Max A Odem, Simran Rahman, Sai S Cheruvu, Xiaodong Cheng, Edgar T Walters, Carmen W Dessauer, Alexis G Bavencoffe

Affiliations

  1. Department of Integrative Biology and Pharmacology, McGovern Medical School at UT Health, Houston, TX 77030, United States.
  2. Department of Diagnostic and Interventional Imaging, McGovern Medical School at UT Health, Houston, TX 77030, United States.

PMID: 31890991 PMCID: PMC6926371 DOI: 10.1016/j.ynpai.2019.100040

Abstract

Chronic pain following spinal cord injury (SCI) is associated with electrical hyperactivity (spontaneous and evoked) in primary nociceptors. Cyclic adenosine monophosphate (cAMP) signaling is an important contributor to nociceptor excitability, and knockdown of the cAMP effector, exchange protein activated by cAMP (EPAC), has been shown to relieve pain-like responses in several chronic pain models. To examine potentially distinct roles of each EPAC isoform (EPAC1 and 2) in maintaining chronic pain, we used rat and mouse models of contusive spinal cord injury (SCI). Pharmacological inhibition of EPAC1 or 2 in a rat SCI model was sufficient to reverse SCI-induced nociceptor hyperactivity, indicating that EPAC1 and 2 signaling activity are complementary, with both required to maintain hyperactivity. However, EPAC activation was not sufficient to induce similar hyperactivity in nociceptors from naïve rats, and we observed no change in EPAC protein expression after SCI. In the mouse SCI model, inhibition of both EPAC isoforms through a combination of pharmacological inhibition and genetic deletion was required to reverse SCI-induced nociceptor hyperactivity. This was consistent with our finding that neither EPAC1

© 2019 The Authors.

Keywords: Depolarizing spontaneous fluctuations; Hyperalgesia; Hyperexcitability; Neuropathic pain; Spontaneous activity; cAMP signaling

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

  1. Horm Behav. 2018 Feb;98:121-129 - PubMed
  2. Pain. 2019 Nov;160(11):2440-2455 - PubMed
  3. Transl Psychiatry. 2016 Sep 06;6(9):e881 - PubMed
  4. Neuropharmacology. 2018 Mar 1;130:18-29 - PubMed
  5. Biochem Pharmacol. 2009 Mar 1;77(5):867-77 - PubMed
  6. J Neurosci. 2012 Aug 22;32(34):11864-78 - PubMed
  7. FASEB J. 2014 Nov;28(11):4617-28 - PubMed
  8. Front Physiol. 2012 Aug 02;3:309 - PubMed
  9. Eur J Pain. 2017 Jan;21(1):29-44 - PubMed
  10. Pain. 2018 May;159(5):884-893 - PubMed
  11. J Neurosci. 2005 Jun 29;25(26):6119-26 - PubMed
  12. Mol Brain. 2015 Jun 24;8:38 - PubMed
  13. Pain. 2016 Jul;157(7):1541-50 - PubMed
  14. J Med Chem. 2013 Feb 14;56(3):952-62 - PubMed
  15. Science. 2011 Sep 9;333(6048):1462-6 - PubMed
  16. J Clin Invest. 2013 Dec;123(12):5023-34 - PubMed
  17. Diabetes. 2013 Aug;62(8):2796-807 - PubMed
  18. Neuron. 2007 Aug 2;55(3):365-76 - PubMed
  19. Nat Commun. 2013;4:1682 - PubMed
  20. J Neurosci Methods. 1994 Jul;53(1):55-63 - PubMed
  21. Anesthesiology. 2017 Jan;126(1):150-162 - PubMed
  22. J Neurosci Methods. 1985 Aug;14(3):149-67 - PubMed
  23. J Neurosci. 2016 Feb 3;36(5):1660-8 - PubMed
  24. Mol Cell Neurosci. 2016 Jan;70:54-67 - PubMed
  25. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3036-41 - PubMed
  26. J Neurophysiol. 2006 Jan;95(1):479-92 - PubMed
  27. Pain. 2014 Sep;155(9):1708-19 - PubMed
  28. Curr Pain Headache Rep. 2012 Jun;16(3):207-16 - PubMed
  29. J Neurol Sci. 2018 Jan 15;384:75-83 - PubMed
  30. Neurobiol Pain. 2019 Mar 08;6:100028 - PubMed
  31. Eur J Pain. 2018 Apr 10;:null - PubMed
  32. J Neurotrauma. 1995 Feb;12(1):1-21 - PubMed
  33. Pain. 1988 Jan;32(1):77-88 - PubMed
  34. J Biol Chem. 2006 Feb 3;281(5):2506-14 - PubMed
  35. Mol Cell Biol. 2013 Mar;33(5):918-26 - PubMed
  36. ACS Med Chem Lett. 2017 Oct 02;8(11):1183-1187 - PubMed
  37. Circulation. 2013 Feb 26;127(8):913-22 - PubMed
  38. J Biol Chem. 2012 Dec 28;287(53):44192-202 - PubMed
  39. PLoS One. 2015 May 01;10(5):e0125022 - PubMed
  40. PLoS One. 2014 Aug 15;9(8):e104529 - PubMed
  41. J Mol Neurosci. 2016 Aug;59(4):554-64 - PubMed
  42. PLoS One. 2017 Mar 9;12(3):e0173085 - PubMed
  43. J Biol Chem. 2004 Feb 27;279(9):7956-61 - PubMed
  44. Brain Res Brain Res Protoc. 1997 Dec 1;2(1):75-84 - PubMed
  45. J Neurotrauma. 2006 May;23(5):635-59 - PubMed
  46. Exp Neurol. 2016 Sep;283(Pt A):365-74 - PubMed
  47. J Neurotrauma. 2010 Nov;27(11):2067-76 - PubMed
  48. Brain Behav Immun. 2013 Oct;33:164-72 - PubMed
  49. Pain. 2003 Jun;103(3):249-57 - PubMed
  50. Philos Trans R Soc Lond B Biol Sci. 2019 Nov 11;374(1785):20190277 - PubMed
  51. Pain. 2018 Nov;159(11):2347-2362 - PubMed
  52. Neuroscience. 2017 Dec 16;366:1-14 - PubMed
  53. Pain. 2010 Dec;151(3):670-9 - PubMed
  54. Neuroscience. 2015 Aug 20;301:121-33 - PubMed
  55. J Neurosci. 2014 Aug 6;34(32):10765-9 - PubMed
  56. Pain. 2013 Dec;154 Suppl 1:S71-6 - PubMed
  57. J Mol Cell Cardiol. 2011 Jan;50(1):87-98 - PubMed
  58. Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19333-8 - PubMed
  59. Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2519-24 - PubMed
  60. J Neurosci. 2010 Nov 3;30(44):14870-82 - PubMed
  61. J Biol Chem. 2013 Feb 8;288(6):3929-37 - PubMed
  62. MMWR Morb Mortal Wkly Rep. 2018 Sep 14;67(36):1001-1006 - PubMed
  63. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18613-8 - PubMed
  64. Mol Cell Neurosci. 2008 Aug;38(4):578-88 - PubMed
  65. J Neurosci Res. 2008 Feb 1;86(2):443-7 - PubMed
  66. Pain. 2013 Oct;154(10):2130-41 - PubMed
  67. PLoS One. 2016 Feb 25;11(2):e0150164 - PubMed
  68. Pain. 2010 Dec;151(3):569-70 - PubMed
  69. Front Behav Neurosci. 2018 Apr 03;12:58 - PubMed
  70. J Neurosci. 2010 Sep 22;30(38):12806-15 - PubMed
  71. Neuron. 2012 Feb 23;73(4):774-88 - PubMed
  72. J Physiol. 2007 Oct 1;584(Pt 1):191-203 - PubMed
  73. Pain. 2018 Jul;159(7):1392-1402 - PubMed

Publication Types

Grant support