title: Brain-derived neurotrophic factor is upregulated in the cervical dorsal root ganglia and spinal cord and contributes to the maintenance of pain from facet joint injury in the rat.
abstract: The facet joint is commonly associated with neck and low back pain and is susceptible to loading-induced injury. Although tensile loading of the cervical facet joint has been associated with inflammation and neuronal hyperexcitability, the mechanisms of joint loading-induced pain remain unknown. Altered brain-derived neurotrophic factor (BDNF) levels are associated with a host of painful conditions, but the role of BDNF in loading-induced joint pain remains undefined. Separate groups of rats underwent a painful cervical facet joint distraction or a sham procedure. Bilateral forepaw mechanical hypersensitivity was assessed and BDNF mRNA and protein levels were quantified in the dorsal root ganglion (DRG) and spinal cord at days 1 and 7. Facet joint distraction induced significant (P < 0.001) mechanical hypersensitivity at both time points. Painful joint distraction did not alter BDNF mRNA in the DRG compared with sham levels but did significantly increase (P < 0.016) BDNF protein expression over sham in the DRG at day 7. Painful distraction also significantly increased BDNF mRNA (P = 0.031) and protein expression (P = 0.047) over sham responses in the spinal cord at day 7. In a separate study, intrathecal administration of the BDNF-sequestering molecule trkB-Fc on day 5 after injury partially attenuated behavioral sensitivity after joint distraction and reduced pERK in the spinal cord at day 7 (P < 0.045). Changes in BDNF after painful facet joint injury and the effect of spinal BDNF sequestration in partially reducing pain suggest that BDNF signaling contributes to the maintenance of loading-induced facet pain but that additional cellular responses are also likely involved.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Jeffrey V
authors.initials: JV
authors.lastname: Kras
authors.forename: Christine L
authors.initials: CL
authors.lastname: Weisshaar
authors.forename: Julia
authors.initials: J
authors.lastname: Quindlen
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002574:Cervical Vertebrae; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*; D015854:Up-Regulation; D021801:Zygapophyseal Joint / Q000293:injuries*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; ERK; facet joint; pain; trkB