RGD Reference Report - The suppression of bone marrow-derived microglia in the amygdala improves the anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice. - Rat Genome Database

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The suppression of bone marrow-derived microglia in the amygdala improves the anxiety-like behavior induced by chronic partial sciatic nerve ligation in mice.

Authors: Sawada, A  Niiyama, Y  Ataka, K  Nagaishi, K  Yamakage, M  Fujimiya, M 
Citation: Sawada A, etal., Pain. 2014 Jun 4. pii: S0304-3959(14)00264-4. doi: 10.1016/j.pain.2014.05.031.
RGD ID: 8661781
Pubmed: PMID:24907405   (View Abstract at PubMed)
DOI: DOI:10.1016/j.pain.2014.05.031   (Journal Full-text)

Chronic neuropathic pain causes abnormal sensitivities such as hyperalgesia and allodynia and emotional abnormalities such as anxiety and depression. While spinal cord microglia are involved in abnormal sensitivity to neuropathic pain, no previous studies have examined the mechanism of neuropathic pain-induced anxiety. Here, we examined the involvement of bone marrow (BM)-derived microglia aggregated in the amygdalae of mice with chronic neuropathic pain in the development of anxiety-like behavior. We prepared partial sciatic nerve ligations (PSNL) in mice that received bone marrow transplantation from green fluorescent protein (GFP)-Tg mice after irradiation with head protection, and examined GFP-positive microglia in the central nuclei of the amygdalae (CeA). On day 28 after PSNL, BM-derived microglia aggregated in the CeA concurrent with anxiety-like behavior. BM-derived microglia in the CeA highly expressed interleukin (IL)-1beta and C-C chemokine receptor type 2 (CCR2). Additionally, neurons in the CeA highly expressed monocyte chemotactic protein-1 (MCP-1), a ligand for CCR2, in PSNL-treated mice compared to sham-operated mice, suggesting that the MCP-1/CCR2 axis is involved in the recruitment of BM-derived microglia. Oral administration of a CCR2 antagonist decreased the number of BM-derived microglia in the CeA, and successfully reversed the anxiety-like behavior and hypersensitivity to mechanical stimuli in PSNL-treated mice. Microinjections of an IL-1beta receptor antagonist directly into the CeA successfully reversed the anxiety-like behavior in the PSNL-treated mice even though the neuropathic pain persisted. These results suggest that the recruitment of BM-derived microglia to the CeA via the MCP-1/CCR2 axis and neuron-microglia interactions might be important in the pathogenesis of neuropathic pain-induced anxiety.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
anxiety disorder  ISOCcr2 (Mus musculus)8661781; 8661781associated with Sciatic NeuropathyRGD 
anxiety disorder  IMP 8661781associated with Sciatic NeuropathyRGD 
Hyperalgesia  ISOCcr2 (Mus musculus)8661781; 8661781associated with Sciatic NeuropathyRGD 
Hyperalgesia  IMP 8661781associated with Sciatic NeuropathyRGD 
sciatic neuropathy  ISOCcr2 (Mus musculus)8661781; 8661781 RGD 
sciatic neuropathy  IEP 8661781 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Mus musculus)
Ccr2  (C-C motif chemokine receptor 2)

Genes (Homo sapiens)
CCR2  (C-C motif chemokine receptor 2)


Additional Information