19 Harley St, London, W1G 9QJ, UK

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

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

Keywords : Animals,Brain-Derived Neurotrophic Factor,Calcitonin,Calcitonin Gene-Related Peptide,Cells,Cultured,chemically induced,China,Culture,Cytokines,cytology,drug effects,Freund’s Adjuvant,Ganglia,Spinal,genetics,Hyperalgesia,immunology,Inflammation,Male,MAP Kinase Signaling System,metabolism,methods,Necrosis,Neurons,Pain,Pain Measurement,pharmacology,physiology,Rats,Rats,Sprague-Dawley,Receptor,trkB,Sensory Receptor Cells,Spinal Cord,Substance P,Taiwan,transmission,TRPV Cation Channels,Tumor Necrosis Factor-alpha,Tyrosine,Universities,Up-Regulation,, Dorsal,Root,Ganglia,Bdnf, antidepressants for nerve pain relief

Date of Publication : 2011 Sep 30

Authors : Lin YT;Ro LS;Wang HL;Chen JC;

Organisation : Department of Physiology and Pharmacology, Chang-Gung University, Taiwan, Republic of China

Journal of Publication : J Neuroinflammation

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/21958434

The London Spine Unit : Harley Street UK. Specialists in Cutting Edge Technologies for Spinal Surgery

Make an Appointment 

Trustpilot Reviews
Doctify Reviews
Top Doctor Reviews

?Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain an in vivo and in vitro study | What is a deep muscle massage

What our patients say ...

Consultant Spine Surgeon
Consultant Spine Surgeon
Consultant Spine Surgeon

This surgical technique consists of a percutaneous approach for the treatment of small to medium size hernias of the intervertebral disc by laser energy. The main objective is to reduce the intradiscal pressure in the nucleus pulposus

Laser Disc Surgery can be performed under local anaesthetic as a day case at our centre on the prestigious Harley Street.
What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

treatment of all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

If you have any emergency Doctor’s need, simply call our 24 hour emergency

Your personal case manager will ensure that you receive the best possible care.

Call Now 

+44 844 589 2020
+44 203 973 8810