title: Intra-articular nerve growth factor regulates development, but not maintenance, of injury-induced facet joint pain & spinal neuronal hypersensitivity.
abstract: OBJECTIVE
  The objective of the current study is to define whether intra-articular nerve growth factor (NGF), an inflammatory mediator that contributes to osteoarthritic pain, is necessary and sufficient for the development or maintenance of injury-induced facet joint pain and its concomitant spinal neuronal hyperexcitability.
  
  
  METHODS
  Male Holtzman rats underwent painful cervical facet joint distraction (FJD) or sham procedures. Mechanical hyperalgesia was assessed in the forepaws, and NGF expression was quantified in the C6/C7 facet joint. An anti-NGF antibody was administered intra-articularly in additional rats immediately or 1 day following facet distraction or sham procedures to block intra-articular NGF and test its contribution to initiation and/or maintenance of facet joint pain and spinal neuronal hyperexcitability. NGF was injected into the bilateral C6/C7 facet joints in separate rats to determine if NGF alone is sufficient to induce these behavioral and neuronal responses.
  
  
  RESULTS
  NGF expression increases in the cervical facet joint in association with behavioral sensitivity after that joint's mechanical injury. Intra-articular application of anti-NGF immediately after a joint distraction prevents the development of both injury-induced pain and hyperexcitability of spinal neurons. Yet, intra-articular anti-NGF applied after pain has developed does not attenuate either behavioral or neuronal hyperexcitability. Intra-articular NGF administered to the facet in naïve rats also induces behavioral hypersensitivity and spinal neuronal hyperexcitability.
  
  
  CONCLUSIONS
  Findings demonstrate that NGF in the facet joint contributes to the development of injury-induced joint pain. Localized blocking of NGF signaling in the joint may provide potential treatment for joint pain.
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: jkras@seas.upenn.edu.
authors.forename: J V
authors.initials: JV
authors.lastname: Kras
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: skartha@seas.upenn.edu.
authors.forename: S
authors.initials: S
authors.lastname: Kartha
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: winkelst@seas.upenn.edu.
authors.forename: B A
authors.initials: BA
authors.lastname: Winkelstein
mesh_terms: D000818:Animals; D018771:Arthralgia / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D010003:Osteoarthritis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D021801:Zygapophyseal Joint / Q000293:injuries / Q000378:metabolism*
chemical_list: D004247:DNA; D020932:Nerve Growth Factor
keywords: Facet joint; NGF; Neuronal hyperexcitability; Pain; Trauma