Contribution of the chemokine (C-C motif) ligand 2 (CCL2) to mechanical hypersensitivity after surgical incision in rats.
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.
Peters
Christopher M
CM
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. chrpeter@wfubmc.edu
Eisenach
James C
JC
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
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2
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