Wednesday, December 19, 2012

CRPS: Neuropeptide deficient mice


thank you, brave and selfless mice of the research world.



Neuropeptide deficient mice have attenuated nociceptive, vascular, and inflammatory changes in a tibia fracture model of complex regional pain syndrome

Tian-Zhi Guo (wxtguo@yahoo.com)

Tzuping Wei (tzupingwei@yahoo.com)
Xiaoyou Shi (xyshi@stanford.edu)
Wen-Wu Li (wenwu.li@gmail.com)
Saiyun Hou (saiyunh@gmail.com)
Liping Wang (lipingwang05@yahoo.com)
Kazutake Tsujikawa (tujikawa@phs.osaka-u.ac.jp)
Kenner C Rice (kennerr@nida.nih.gov)
Kejun Cheng (kejunch@mail.nih.gov)
David J Clark (David.Clark5@va.gov)
Wade S Kingery (wkingery@stanford.edu)


Molecular Pain 2012, 8:85 doi:10.1186/1744-8069-8-85
Published: 28 November 2012

Abstract (provisional)

Background
Distal limb fracture in man can induce a complex regional pain syndrome (CRPS) with pain, warmth, edema, and cutaneous inflammation. In the present study substance P (SP, Tac1-/-) and CGRP receptor (RAMP1-/-) deficient mice were used to investigate the contribution of neuropeptide signaling to CRPS-like changes in a tibia fracture mouse model. Wildtype, Tac1-/-, and RAMP1-/- mice underwent tibia fracture and casting for 3 weeks, then the cast was removed and hindpaw mechanical allodynia, unweighting, warmth, and edema were tested over time. Hindpaw skin was collected at 3 weeks post-fracture for immunoassay and femurs were collected for micro-CT analysis.

Results
Wildtype mice developed hindpaw allodynia, unweighting, warmth, and edema at 3 weeks post-fracture, but in the Tac1-/- fracture mice allodynia and unweighting were attenuated and there was no warmth and edema. RAMP1-/- fracture mice had a similar presentation, except there was no reduction in hindpaw edema. Hindpaw skin TNFalpha, IL-1beta, IL-6 and NGF levels were up-regulated in wildtype fracture mice at 3 weeks post-fracture, but in the Tac1-/- and RAMP1-/- fracture mice only IL-6 was increased. The epidermal keratinocytes were the cellular source for these inflammatory mediators. An IL-6 receptor antagonist partially reversed post-fracture pain behaviors in wildtype mice.

Conclusions
In conclusion, both SP and CGRP are critical neuropeptide mediators for the pain behaviors, vascular abnormalities, and up-regulated innate immune responses observed in the fracture hindlimb. We postulate that the residual pain behaviors observed in the Tac1-/- and RAMP1-/- fracture mice are attributable to the increased IL-6 levels observed in the hindpaw skin after fracture.

Some related articles on PubMed:


Li WW, Sabsovich I, Guo TZ, Zhao R, Kingery WS, Clark JD.
Pain. 2009 Aug;144(3):303-13. doi: 10.1016/j.pain.2009.04.033. Epub 2009 May 26.
PMID:
 
19473768
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
3.
Li WW, Guo TZ, Li XQ, Kingery WS, Clark JD.
Pain. 2010 Dec;151(3):843-52. doi: 10.1016/j.pain.2010.09.026. Epub 2010 Oct 12.
PMID:
 
20934254
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
4.
Wei T, Li WW, Guo TZ, Zhao R, Wang L, Clark DJ, Oaklander AL, Schmelz M, Kingery WS.
Pain. 2009 Aug;144(3):278-86. doi: 10.1016/j.pain.2009.04.020. Epub 2009 May 21.
PMID:
 
19464118
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
5.
Wei T, Guo TZ, Li WW, Hou S, Kingery WS, Clark JD.
J Neuroinflammation. 2012 Jul 23;9:181.
PMID:
 
22824437
 
[PubMed - in process] 
Free PMC Article
6.
Guo TZ, Wei T, Kingery WS.
Pain. 2006 Mar;121(1-2):158-67. Epub 2006 Feb 10.
PMID:
 
16472917
 
[PubMed - indexed for MEDLINE]
7.
Shi X, Wang L, Li X, Sahbaie P, Kingery WS, Clark JD.
Anesth Analg. 2011 Jul;113(1):175-83. doi: 10.1213/ANE.0b013e31821a0258. Epub 2011 May 19.
PMID:
 
21596883
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
8.
Guo TZ, Offley SC, Boyd EA, Jacobs CR, Kingery WS.
Pain. 2004 Mar;108(1-2):95-107.
PMID:
 
15109512
 
[PubMed - indexed for MEDLINE]
9.
Li WW, Guo TZ, Liang D, Shi X, Wei T, Kingery WS, Clark JD.
Pain. 2009 Dec 15;147(1-3):277-86. doi: 10.1016/j.pain.2009.09.032. Epub 2009 Oct 22.
PMID:
 
19853379
 
[PubMed - indexed for MEDLINE]
10.
Sabsovich I, Wei T, Guo TZ, Zhao R, Shi X, Li X, Yeomans DC, Klyukinov M, Kingery WS, Clark JD.
Pain. 2008 Aug 15;138(1):47-60. Epub 2008 Feb 20.
PMID:
 
18083307
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
11.
Sabsovich I, Guo TZ, Wei T, Zhao R, Li X, Clark DJ, Geis C, Sommer C, Kingery WS.
Pain. 2008 Jul 31;137(3):507-19. Epub 2007 Nov 26.
PMID:
 
18035493
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
12.
Kingery WS, Davies MF, Clark JD.
Pain. 2003 Jul;104(1-2):75-84.
PMID:
 
12855316
 
[PubMed - indexed for MEDLINE]
13.
Sahbaie P, Shi X, Guo TZ, Qiao Y, Yeomans DC, Kingery WS, Clark JD.
Pain. 2009 Oct;145(3):341-9. doi: 10.1016/j.pain.2009.06.037. Epub 2009 Aug 5.
PMID:
 
19660865
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
14.
Wei T, Sabsovich I, Guo TZ, Shi X, Zhao R, Li W, Geis C, Sommer C, Kingery WS, Clark DJ.
Eur J Pain. 2009 Mar;13(3):253-62. doi: 10.1016/j.ejpain.2008.04.014. Epub 2008 Jun 12.
PMID:
 
18554967
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
15.
Kingery WS, Guo T, Agashe GS, Davies MF, Clark JD, Maze M.
Brain Res. 2001 Sep 21;913(2):140-8.
PMID:
 
11549377
 
[PubMed - indexed for MEDLINE]
17.
Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ.
Br J Pharmacol. 1995 Aug;115(7):1265-75.
PMID:
 
7582555
 
[PubMed - indexed for MEDLINE] 
Free PMC Article
18.
Li WW, Guo TZ, Liang DY, Sun Y, Kingery WS, Clark JD.
Anesthesiology. 2012 Apr;116(4):882-95. doi: 10.1097/ALN.0b013e31824bb303.
PMID:
 
22343473
 
[PubMed - indexed for MEDLINE] 
Free Article
19.
Siegel SM, Lee JW, Oaklander AL.
Anesth Analg. 2007 Dec;105(6):1820-9, table of contents.
PMID:
 
18042888
 
[PubMed - indexed for MEDLINE] 
Free Article
20.
Hou Q, Barr T, Gee L, Vickers J, Wymer J, Borsani E, Rodella L, Getsios S, Burdo T, Eisenberg E, Guha U, Lavker R, Kessler J, Chittur S, Fiorino D, Rice F, Albrecht P.
Pain. 2011 Sep;152(9):2036-51. doi: 10.1016/j.pain.2011.04.033. Epub 2011 Jun 17.
PMID:
 
21641113
 
[PubMed - indexed for MEDLINE] 
Free PMC Article


    No comments:

    Post a Comment

    The Haddock Corporation's newest dictate: Anonymous comments are no longer allowed. It is easy enough to register and just takes a moment. We look forward to hearing from you non-bots and non-spammers!