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.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Peters CM,Eisenach JC

doi

10.1097/ALN.0b013e3181d3d978

subject

Has Abstract

pub_date

2010-05-01 00:00:00

pages

1250-8

issue

5

eissn

0003-3022

issn

1528-1175

journal_volume

112

pub_type

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