RGD Reference Report - Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation. - Rat Genome Database
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Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation.

Authors: Guo, W  Wang, H  Zou, S  Dubner, R  Ren, K 
Citation: Guo W, etal., Neurosci Bull. 2012 Apr;28(2):193-207. doi: 10.1007/s12264-012-1218-6.
RGD ID: 8549494
Pubmed: (View Article at PubMed) PMID:22466130
DOI: Full-text: DOI:10.1007/s12264-012-1218-6

OBJECTIVE: Despite accumulating evidence on a role of immune cells and their associated chemicals in mechanisms of pain, few studies have addressed the potential role of chemokines in the descending facilitation of persistent pain. The present study was undertaken to test the hypothesis that the chemokine (C-C motif) ligand 2 (CCL2) (commonly known as monocyte chemoattractant protein-1) signaling in the rostral ventromedial medulla (RVM), a pivotal structure in brainstem pain modulatory circuitry, is involved in descending pain facilitation in rats. METHODS: An L5 spinal nerve ligation (SNL) was produced in rats under pentobarbital anesthesia. Western blot and immunohistochemistry were used to detect the expression levels of CCL2 and CCL2 receptor (CCR2), and examine their distributions compared with the neuronal marker NeuN as well as glial markers glial fibrillary acidic protein (GFAP, astroglial) and CD11b (microglial), respectively. RESULTS: SNL induced an increase in CCL2 expression in the RVM, and this returned to the control level at 4 weeks after injury. The induced CCL2 colocalized with NeuN, but not with GFAP and CD11b. CCR2 was also upregulated by SNL in the RVM, and this increase lasted for at least 4 weeks. CCR2 was colocalized with CD11b but not GFAP. Few RVM neurons also exhibited CCR2 staining. Neutralizing CCL2 with an anti-CCL2 antibody (0.2-20 ng) or injecting RS-102895 (0.1-10 pmol), a CCR2b chemokine receptor antagonist, into the RVM on day 1 after SNL, significantly attenuated the established thermal and mechanical hypersensitivity. In addition, injection of recombinant rat CCL2 (0.03-3 pmol) into the RVM induced dose-dependent hyperalgesia, which was prevented by pretreatment with RS-102895 (10 pmol). Interleukin-1beta (IL-1beta), a potent inducer of neuronal CCL2, was also selectively upregulated in RVM reactive astrocytes. Injection of IL-1beta (120 fmol) into the RVM induced behavioral hyperalgesia, which was blocked by RS-102895 (10 pmol). However, an IL-1 receptor antagonist (3 pmol) did not prevent CCL2 (3 pmol)-induced hyperalgesia. These results suggest that the effect of CCL2 is downstream to IL-1beta signaling. CONCLUSION: The IL-1beta and CCL2-CCR2 signaling cascades play a role in neuron-glia-cytokine interactions and the descending facilitation of neuropathic pain.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Ccl2  (C-C motif chemokine ligand 2)

Genes (Mus musculus)
Ccl2  (chemokine (C-C motif) ligand 2)

Genes (Homo sapiens)
CCL2  (C-C motif chemokine ligand 2)

Objects referenced in this article
0 CCL13 C-C motif chemokine ligand 13 All species

Additional Information