title: Painful Cervical Facet Joint Injury Is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Differentially Relate to Local Tissue Injury Severity.
abstract: METHODS
  Immunohistochemistry labeled pre- and postsynaptic structural markers to quantify excitatory and inhibitory synapses in the spinal superficial dorsal horn at 14 days after painful facet joint injury in the rat.
  
  
  OBJECTIVE
  The objective of this study was to investigate the relationship between pain and synapse density in the spinal cord after facet injury.
  
  
  BACKGROUND
  Neck pain is a major contributor to disability and often becomes chronic. The cervical facet joints are susceptible to loading-induced painful injury, initiating spinal central sensitization responses. Although excitatory synapse plasticity has been reported in the superficial dorsal horn early after painful facet injury, whether excitatory and/or inhibitory synapse density is altered at a time when pain is maintained is unknown.
  
  
  METHODS
  Rats underwent either a painful C6/C7 facet joint distraction or sham surgery. Mechanical hyperalgesia was measured and immunohistochemistry techniques for synapse quantification were used to quantify excitatory and inhibitory synapse densities in the superficial dorsal horn at day 14. Logarithmic correlation analyses evaluated whether the severity of facet injury correlated with either behavioral or synaptic outcomes.
  
  
  RESULTS
  Facet joint injury induces pain that is sustained until day 14 (P <0.001) and both significantly greater excitatory synapse density (P = 0.042) and lower inhibitory synapse density (P = 0.0029) in the superficial dorsal horn at day 14. Injury severity is significantly correlated with pain at days 1 (P = 0.0011) and 14 (P = 0.0002), but only with inhibitory, not excitatory, synapse density (P = 0.0025) at day 14.
  
  
  CONCLUSIONS
  This study demonstrates a role for structural plasticity in both excitatory and inhibitory synapses in the maintenance of facet-mediated joint pain, and that altered inhibitory, but not excitatory, synapse density correlates to the severity of painful joint injury. Understanding the functional consequences of this spinal structural plasticity is critical to elucidate mechanisms of chronic joint pain.
  
  
  METHODS
  N /A.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA.
authors.forename: Meagan E
authors.initials: ME
authors.lastname: Ita
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Crosby
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Bulka
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA.|Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D018771:Arthralgia / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D002574:Cervical Vertebrae / Q000293:injuries / Q000294:innervation*; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D019547:Neck Pain / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D066148:Spinal Cord Dorsal Horn / Q000503:physiopathology*; D055366:Synaptic Potentials / Q000502:physiology*; D021801:Zygapophyseal Joint / Q000293:injuries / Q000294:innervation*