Display options
Share it on

Int J Clin Exp Med. 2015 Feb 15;8(2):2065-76. eCollection 2015.

Paroxetine alleviates rat limb post-ischemia induced allodynia through GRK2 upregulation in superior cervical ganglia.

International journal of clinical and experimental medicine

Jun Tang, Jing Dong, Li Yang, Lingqi Gao, Jijian Zheng

Affiliations

  1. Department of Anesthesiology, Jinshan Hospital, Fudan University Shanghai, China.
  2. Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital 650 Xin Songjiang Road, Shanghai 201620, China.

PMID: 25932137 PMCID: PMC4402784

Abstract

Long-lasting neuroplastic changes induced by transient decrease in G protein-coupled receptor kinase 2 (GRK2) in nociceptors enhances and prolongs inflammatory hyperalgesia. Here, we investigated the effects of paroxetine (a selective serotonin reuptake inhibitor and GRK2 inhibitor) on GRK2 expression in superior cervical ganglion (SCG) in a rat model of complex regional pain syndrome type I (CRPS-I). After ischemia-reperfusion (I/R) injury, the ipsilateral 50% paw withdrawal thresholds (PWTs) to mechanical stimuli and the expression levels of GRK2 protein and mRNA in the ipsilateral SCGs all decreased significantly; the ipsilateral cold allodynia scores increased significantly. No significant differences were found in the contralateral side except GRK2 mRNA reduced significantly at day 2-day 9 after I/R injury, but still higher than those in ipsilateral SCGs. After paroxetine administration, the ipsilateral 50% PWTs at day 2, 7, 14, and 21 were significantly higher than those in control group; The GRK2 protein and mRNA levels in ipsilateral SCGs were also significantly up-regulated after day1; The ipsilateral cold allodynia scores were significantly reduced after day7. No significant differences were found in the contralateral 50% PWTs, cold allodynia scores, and GRK2 protein level except GRK2 mRNA levels increased significantly at day1-day7 after paroxetine administration. Therefore, a transient decrease of GRK2 expression in SCG neurons might be involved in the development and maintenance of allodynia in CRPS-I and paroxetine might alleviate this allodynia through GRK2 protein upregulation in SCGs.

Keywords: G protein-coupled receptor kinase 2; complex regional pain syndrome type I; mechanical and cold allodynia; paroxetine; selective serotonin reuptake inhibitor; superior cervical ganglion neurons

References

  1. Brain Behav Immun. 2011 Aug;25(6):1055-60 - PubMed
  2. N Engl J Med. 1992 May 7;326(19):1250-6 - PubMed
  3. Mol Pharmacol. 2001 Dec;60(6):1243-53 - PubMed
  4. J Clin Pharmacol. 2012 Jan;52(1):6-17 - PubMed
  5. Neurosci Lett. 1990 Jul 17;115(1):62-7 - PubMed
  6. J Immunol. 2005 Apr 1;174(7):4400-6 - PubMed
  7. Pain. 2004 May;109(1-2):150-61 - PubMed
  8. Pain. 1991 Jun;45(3):309-20 - PubMed
  9. Annu Rev Pharmacol Toxicol. 1980;20:441-62 - PubMed
  10. Auton Neurosci. 2014 May;182:102-7 - PubMed
  11. J Neurosci Methods. 1994 Jul;53(1):55-63 - PubMed
  12. Iran Biomed J. 2014;18(2):94-100 - PubMed
  13. J Biol Chem. 2002 Jul 12;277(28):25266-72 - PubMed
  14. Curr Pain Headache Rep. 2010 Jun;14(3):196-202 - PubMed
  15. Neurosci Res. 2009 Jan;63(1):42-6 - PubMed
  16. Brain Res Mol Brain Res. 2003 Mar 17;111(1-2):31-41 - PubMed
  17. Exp Neurol. 2000 Feb;161(2):740-4 - PubMed
  18. Brain Res. 1991 Nov 29;565(2):237-46 - PubMed
  19. Autoimmun Rev. 2014 Mar;13(3):242-65 - PubMed
  20. Pain. 2010 Sep;150(3):550-60 - PubMed
  21. Eur J Pharmacol. 2008 Mar 31;583(1):97-102 - PubMed
  22. J Neurosci. 2010 Sep 22;30(38):12806-15 - PubMed
  23. Pain Med. 2007 May-Jun;8(4):326-31 - PubMed
  24. EMBO J. 2003 Aug 1;22(15):3816-24 - PubMed
  25. Int J Neuropsychopharmacol. 2010 Feb;13(1):83-91 - PubMed
  26. J Neurosci. 2010 Feb 10;30(6):2138-49 - PubMed
  27. Neuroreport. 2013 Feb 13;24(3):137-41 - PubMed
  28. Pain. 2004 Nov;112(1-2):94-105 - PubMed
  29. ACS Chem Biol. 2012 Nov 16;7(11):1830-9 - PubMed
  30. J Psychiatry Neurosci. 2001 Jan;26(1):30-6 - PubMed
  31. Neuroscience. 1995 Feb;64(3):751-67 - PubMed
  32. Pain Med. 2013 Feb;14(2):180-229 - PubMed
  33. Nat Rev Neurol. 2014 Sep;10(9):518-28 - PubMed
  34. Pain. 1990 Aug;42(2):135-44 - PubMed
  35. Pain. 2012 Jun;153(6):1187-92 - PubMed
  36. Am J Med. 2001 Jul;111(1):54-63 - PubMed
  37. J Psychiatry Neurosci. 2001 Jan;26(1):21-9 - PubMed
  38. Pain. 2006 Mar;121(1-2):158-67 - PubMed
  39. FASEB J. 1999 Apr;13(6):715-25 - PubMed
  40. Neuroreport. 2011 Dec 21;22(18):984-8 - PubMed
  41. Trends Pharmacol Sci. 2006 Jul;27(7):348-54 - PubMed
  42. Pharmacol Rev. 1986 Sep;38(3):179-226 - PubMed
  43. J Mol Signal. 2014 Mar 06;9(1):1 - PubMed
  44. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409 - PubMed
  45. Neuroscience. 2012 Oct 11;222:392-403 - PubMed
  46. J Biol Chem. 2009 Aug 28;284(35):23444-53 - PubMed
  47. Pain Pract. 2006 Mar;6(1):27-33 - PubMed

Publication Types