Format

Send to

Choose Destination
See comment in PubMed Commons below
Pain. 2004 Sep;111(1-2):125-35.

Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation.

Author information

1
Division of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.

Abstract

Group I metabotropic glutamate receptors (mGluRs) and their downstream signaling pathways, which involve the extracellular signal-regulated kinases (ERKs), have been implicated as mediators of plasticity in several pain models. In this study, we report that inflammation leads to a long-lasting enhancement of behavioral responses induced by activation of spinal group I mGluRs. Thus, the nocifensive response to intrathecal injection of the group I mGluR agonist (RS)-3,5-Dihydroxyphenylglycine (DHPG) is significantly potentiated seven days following Complete Freund's Adjuvant (CFA)-induced inflammation of the hind paw. This potentiation is not associated with increased mGlu1 or mGlu5 receptor expression but is associated with increased levels of phosphorylated ERK in dorsal horn neurons. We also tested whether the increased behavioral response to DHPG following inflammation may be explained by enhanced coupling of the group I mGluRs to ERK activation. DHPG-induced ERK phosphorylation in the dorsal horn is not potentiated following inflammation. However, inhibiting ERK activation using a MEK inhibitor, U0126, following inflammation attenuates the intrathecal DHPG-induced behavioral responses to a greater extent than in control animals. The results from this study indicate that persistent ERK activation is required for the enhanced behavioral responses to spinal group I mGluR activation following inflammation and suggest that tonic modulation of ERK activity may underlie a component of central sensitization in dorsal horn neurons.

PMID:
15327816
DOI:
10.1016/j.pain.2004.06.009
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Wolters Kluwer
    Loading ...
    Support Center