RGD Reference Report - NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain. - Rat Genome Database

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NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain.

Authors: Kim, D  You, B  Jo, EK  Han, SK  Simon, MI  Lee, SJ 
Citation: Kim D, etal., Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14851-6. doi: 10.1073/pnas.1009926107. Epub 2010 Aug 2.
RGD ID: 11040629
Pubmed: PMID:20679217   (View Abstract at PubMed)
PMCID: PMC2930447   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.1009926107   (Journal Full-text)

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia  ISOCybb (Mus musculus)11040629; 11040629associated with Spinal Cord InjuriesRGD 
Hyperalgesia  IMP 11040629associated with Spinal Cord InjuriesRGD 
Spinal Cord Injuries  ISOCybb (Mus musculus)11040629; 11040629mRNA and protein:increased expression:microglia:RGD 
Spinal Cord Injuries  IEP 11040629mRNA and protein:increased expression:microglia:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cybb  (cytochrome b-245 beta chain)

Genes (Mus musculus)
Cybb  (cytochrome b-245, beta polypeptide)

Genes (Homo sapiens)
CYBB  (cytochrome b-245 beta chain)


Additional Information