title: Contribution of the chemokine (C-C motif) ligand 2 (CCL2) to mechanical hypersensitivity after surgical incision in rats.
abstract: BACKGROUND
  Neural glial signaling in the spinal cord may underlie pain and sensitization after peripheral injury. The authors test the role of a glial activator, the chemokine (C-C motif) ligand 2 (CCL2), on mechanical hypersensitivity after plantar incision in a rat model of postoperative pain.
  
  
  METHODS
  Twenty-four hours after hind paw incision, rats were intrathecally administered an anti-CCL2 neutralizing antibody (3 and 10 microg) or control immunoglobulin G (10 microg). Mechanical hypersensitivity was assessed acutely and for several days after administration of anti-CCL2 antibody using von Frey filaments. Immunohistochemical analysis was conducted on spinal cord sections to examine the effects of treatment on measures of microglial activation, including levels of ionized calcium-binding adaptor molecule 1 and phosphorylated p38 mitogen-activated protein kinase.
  
  
  RESULTS
  Neutralization of spinal CCL2 acutely reversed mechanical hypersensitivity within 30 min in a dose-dependent manner. A single administration also produced a sustained decrease in mechanical hypersensitivity 48 and 72 h after incision. Anti-CCL2 antibody reduced microglial activation as measured by the levels of ionized calcium-binding adaptor molecule 1 immunoreactivity and the number of microglia containing phosphorylated p38 mitogen-activated protein kinase 48 h after incision but not within 30 min of administration.
  
  
  CONCLUSIONS
  These results provide evidence that CCL2 contributes to the maintenance of mechanical hypersensitivity after plantar incision and establish a role for neural glial signaling in postoperative pain. The long-term effects of anti-CCL2 treatment correlate with reduced microglial activation. Spinal blockade of CCL2 may serve as a useful therapy for the treatment of certain aspects of postoperative pain.
authors.affiliation: Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. chrpeter@wfubmc.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Peters
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006614:Hindlimb / Q000503:physiopathology / Q000601:surgery; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D010147:Pain Measurement / Q000379:methods*; D010149:Postoperative Pain / Q000473:pathology / Q000503:physiopathology*; D010812:Physical Stimulation / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013979:Tibial Nerve / Q000378:metabolism / Q000473:pathology / Q000502:physiology
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2
references.citation: J Neurosci. 2009 Jun 24;29(25):8051-62
references.pmid: 19553445
references.citation: Pain. 2003 Jul;104(1-2):15-23
references.pmid: 12855310
references.citation: Pain. 1996 Mar;64(3):493-502
references.pmid: 8783314
references.citation: Mol Pain. 2007 Nov 01;3:33
references.pmid: 17974036
references.citation: Anesth Analg. 2004 Nov;99(5):1453-1460
references.pmid: 15502048
references.citation: Neuroreport. 2003 Jun 11;14(8):1153-7
references.pmid: 12821799
references.citation: Anesth Analg. 2003 Aug;97(2):534-540
references.pmid: 12873949
references.citation: Anesth Analg. 2005 May;100(5):1390-1393
references.pmid: 15845692
references.citation: Neuroreport. 2008 Jan 22;19(2):183-6
references.pmid: 18185105
references.citation: J Neurochem. 2008 Jul;106(2):757-69
references.pmid: 18419759
references.citation: Neurosci Res. 2004 Apr;48(4):463-9
references.pmid: 15041200
references.citation: J Neurosci Res. 2005 Oct 1;82(1):51-62
references.pmid: 16047385
references.citation: J Pain. 2006 Nov;7(11):816-22
references.pmid: 17074623
references.citation: Eur J Pain. 2009 Mar;13(3):263-72
references.pmid: 18554968
references.citation: J Neurochem. 2005 Nov;95(4):1023-34
references.pmid: 16150057
references.citation: Brain Res Rev. 2009 Apr;60(1):125-34
references.pmid: 19146875
references.citation: Eur J Neurosci. 2005 Nov;22(10):2431-40
references.pmid: 16307586
references.citation: J Neurosci Methods. 1994 Jul;53(1):55-63
references.pmid: 7990513
references.citation: J Neurochem. 2003 Sep;86(6):1534-44
references.pmid: 12950462
references.citation: Anesthesiology. 2009 Sep;111(3):640-8
references.pmid: 19672178
references.citation: Brain Res. 2008 Jul 11;1219:116-26
references.pmid: 18538310
references.citation: Lancet. 2008 Jul 12;372(9633):139-44
references.pmid: 18582931
references.citation: Curr Opin Anaesthesiol. 2008 Oct;21(5):580-5
references.pmid: 18784482
references.citation: Anesthesiology. 2006 Mar;104(3):426-31
references.pmid: 16508388
references.citation: Mol Pain. 2007 Dec 12;3:38
references.pmid: 18076762
references.citation: Nat Neurosci. 2007 Nov;10(11):1361-8
references.pmid: 17965656
references.citation: Anesthesiology. 2009 Jan;110(1):155-65
references.pmid: 19104183
references.citation: Anesthesiology. 2007 Apr;106(4):787-94
references.pmid: 17413917
references.citation: J Neurosci. 2007 Nov 7;27(45):12396-406
references.pmid: 17989304
references.citation: Anesth Analg. 2002 Sep;95(3):627-34, table of contents
references.pmid: 12198050
references.citation: J Neurochem. 2005 Mar;92(6):1508-20
references.pmid: 15748168
references.citation: Anesth Analg. 2008 Apr;106(4):1288-95, table of contents
references.pmid: 18349208
references.citation: Anesthesiology. 2004 Jul;101(1):191-203
references.pmid: 15220791
references.citation: J Neurochem. 2006 May;97(3):772-83
references.pmid: 16524371
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7947-52
references.pmid: 12808141
references.citation: J Neurosci. 2009 Apr 1;29(13):4096-108
references.pmid: 19339605
references.citation: J Clin Anesth. 2004 May;16(3):200-6
references.pmid: 15217660
references.citation: Pain. 2005 May;115(1-2):71-83
references.pmid: 15836971