title: Painful facet joint injury induces neuronal stress activation in the DRG: implications for cellular mechanisms of pain.
abstract: The cervical facet joint is implicated as one of the most common sources of chronic neck pain, owing to its rich nociceptive innervation and susceptibility to injurious mechanical loading. Injuries to the facet joint and its ligament can induce inflammation in the joint and spinal cord. Inflammatory molecules which are known to have a role in pain can also stimulate the integrated stress response (ISR). Therefore, we hypothesize that ISR is activated by facet joint injury in a rodent model of pain. To address this hypothesis, we assessed the expression of binding protein (BiP) (also known as growth-related protein 78 (GRP78)), a marker of endoplasmic reticulum stress response, in the dorsal root ganglion (DRG) after painful facet joint injury. In a rodent model of facet joint injury, dynamic distraction of the C6/C7 joint (injury, n=12) was imposed; sham procedures were performed separately (sham, n=8). Forepaw mechanical allodynia was assessed postoperatively for 7 days as a quantitative measure of pain symptoms. The C6 DRG was harvested and assessed for BiP expression using triple label immunofluorescent confocal microscopy and immunoblot analyses. BiP was significantly higher (p<0.001) in the DRG after injury than sham and was expressed predominantly in neurons. Similarly, quantification of BiP by immunoblot demonstrated a significant 2.1-fold increase (p=0.03) in injury compared to sham at day 7. Findings suggest neuronal stress activation is associated with painful facet joint injury, and that joint loading may directly mediate the behavior of DRG neurons in this class of injury.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Dong
authors.forename: Akinleye O
authors.initials: AO
authors.lastname: Odeleye
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Jordan-Sciutto
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D015151:Immunoblotting; D008297:Male; D018832:Molecular Chaperones / Q000096:biosynthesis; D009474:Neurons / Q000378:metabolism*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D013312:Stress, Physiological; D021801:Zygapophyseal Joint / Q000293:injuries* / Q000294:innervation; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP