RGD Reference Report - Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study. - Rat Genome Database

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Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study.

Authors: Lin, YT  Ro, LS  Wang, HL  Chen, JC 
Citation: Lin YT, etal., J Neuroinflammation. 2011 Sep 30;8:126. doi: 10.1186/1742-2094-8-126.
RGD ID: 8657122
Pubmed: PMID:21958434   (View Abstract at PubMed)
PMCID: PMC3203068   (View Article at PubMed Central)
DOI: DOI:10.1186/1742-2094-8-126   (Journal Full-text)

BACKGROUND: During inflammation, immune cells accumulate in damaged areas and release pro-inflammatory cytokines and neurotrophins. Brain-derived neurotrophic factor (BDNF) plays a neuromodulatory role in spinal cord dorsal horn via the post-synaptic tyrosine protein kinase B (trkB) receptor to facilitate pain transmission. However, the precise role of BDNF and trkB receptor in the primary sensory neurons of dorsal root ganglia (DRG) during inflammation remains to be clarified. The aim of this study was to investigate whether and how BDNF-trkB signaling in the DRG is involved in the process of inflammatory pain. METHODS: We used complete Freund's adjuvant- (CFA-) induced and tumor necrosis factor-alpha- (TNF-alpha-) induced inflammation in rat hindpaw as animal models of inflammatory pain. Quantification of protein and/or mRNA levels of pain mediators was performed in separate lumbar L3-L5 DRGs. The cellular mechanism of TNF-alpha-induced BDNF and/or trkB receptor expression was examined in primary DRG cultures collected from pooled L1-L6 DRGs. Calcitonin gene-related peptide (CGRP), BDNF and substance P release were also evaluated by enzyme immunoassay. RESULTS: CFA injection into rat hindpaw resulted in mechanical hyperalgesia and significant increases in levels of TNF-alpha in the inflamed tissues, along with enhancement of BDNF and trkB receptor as well as the pain mediators CGRP and transient receptor potential vanilloid receptor subtype 1 (TRPV1) in DRG. Direct injection of TNF-alpha into rat hindpaw resulted in similar effects with retrograde transport of TNF-alpha along the saphenous nerve to DRG during CFA-induced inflammation. Primary DRG cultures chronically treated with TNF-alpha showed significant enhancement of mRNA and protein levels of BDNF and trkB receptor, BDNF release and trkB-induced phospho-ERK1/2 signal. Moreover, CGRP and substance P release were enhanced in DRG cultures after chronic TNF-alpha treatment or acute BDNF stimulation. In addition, we found that BDNF up-regulated trkB expression in DRG cultures. CONCLUSIONS: Based on our current experimental results, we conclude that inflammation and TNF-alpha up-regulate the BDNF-trkB system in DRG. This phenomenon suggests that up-regulation of BDNF in DRG may, in addition to its post-synaptic effect in spinal dorsal horn, act as an autocrine and/or paracrine signal to activate the pre-synaptic trkB receptor and regulate synaptic excitability in pain transmission, thereby contributing to the development of hyperalgesia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hyperalgesia  ISOBdnf (Rattus norvegicus)8657122; 8657122associated with inflammation and protein:increased expression:dorsal root ganglion:RGD 
Hyperalgesia  IEP 8657122; 8657122; 8657122; 8657122associated with inflammation and protein:increased expression:dorsal root ganglion:RGD 
Hyperalgesia  ISOCalca (Rattus norvegicus)8657122; 8657122associated with inflammation and protein:increased expression:dorsal root ganglion:RGD 
Hyperalgesia  ISONtrk2 (Rattus norvegicus)8657122; 8657122associated with inflammation and protein:increased expression:dorsal root ganglion:RGD 
Hyperalgesia  ISOTrpv1 (Rattus norvegicus)8657122; 8657122associated with inflammation and protein:increased expression:dorsal root ganglion:RGD 
Inflammation  ISOCalca (Rattus norvegicus)8657122; 8657122protein:increased expression:hindpaw:RGD 
Inflammation  IEP 8657122; 8657122; 8657122protein:increased expression:hindpaw:RGD 
Inflammation  ISONtrk2 (Rattus norvegicus)8657122; 8657122protein:increased expression:hindpaw:RGD 
Inflammation  ISOTrpv1 (Rattus norvegicus)8657122; 8657122protein:increased expression:hindpaw:RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Bdnf  (brain-derived neurotrophic factor)
Calca  (calcitonin-related polypeptide alpha)
Ntrk2  (neurotrophic receptor tyrosine kinase 2)
Trpv1  (transient receptor potential cation channel, subfamily V, member 1)

Genes (Mus musculus)
Bdnf  (brain derived neurotrophic factor)
Calca  (calcitonin/calcitonin-related polypeptide, alpha)
Ntrk2  (neurotrophic tyrosine kinase, receptor, type 2)
Trpv1  (transient receptor potential cation channel, subfamily V, member 1)

Genes (Homo sapiens)
BDNF  (brain derived neurotrophic factor)
CALCA  (calcitonin related polypeptide alpha)
NTRK2  (neurotrophic receptor tyrosine kinase 2)
TRPV1  (transient receptor potential cation channel subfamily V member 1)


Additional Information