title: Changes in rat spinal cord gene expression after inflammatory hyperalgesia of the joint and manual therapy.
abstract: BACKGROUND
  Mobilization of a joint affects local tissue directly but may also have other effects that are mediated through the central nervous system.
  
  
  OBJECTIVE
  To identify differential gene expression in the spinal cords of rats with or without inflammatory joint injury after manual therapy or no treatment.
  
  
  METHODS
  Rats were randomly assigned to 1 of 4 treatment groups: no injury and no touch (NI/NT), injury and no touch (I/NT), no injury and manual therapy (NI/MT), and injury and manual therapy (I/MT). We induced acute inflammatory joint injury in the rats by injecting carrageenan into an ankle. Rats in the no-injury groups did not receive carrageenan injection. One day after injury, rats received manual therapy to the knee of the injured limb. Rats in the no-touch groups were anesthetized without receiving manual therapy. Spinal cords were harvested 30 minutes after therapy or no touch, and spinal cord gene expression was analyzed by microarray for 3 comparisons: NI/NT vs I/NT, I/MT vs I/NT, and NI/NT vs NI/MT.
  
  
  RESULTS
  Three rats were assigned to each group. Of 38,875 expressed sequence tags, 755 were differentially expressed in the NI/NT vs I/NT comparison. For the other comparisons, no expressed sequence tags were differentially expressed. Cluster analysis revealed that the differentially expressed sequence tags were over-represented in several categories, including ion homeostasis (enrichment score, 2.29), transmembrane (enrichment score, 1.55), and disulfide bond (enrichment score, 2.04).
  
  
  CONCLUSIONS
  An inflammatory injury to the ankle of rats caused differential expression of genes in the spinal cord. Consistent with other studies, genes involved in ion transport were among those affected. However, manual therapy to the knees of injured limbs or to rats without injury did not alter gene expression in the spinal cord. Thus, evidence for central nervous system mediation of manual therapy was not observed.
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study rachel@ruhlendavis.org.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Ruhlen
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Vineet K
authors.initials: VK
authors.lastname: Singh
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Vanessa K
authors.initials: VK
authors.lastname: Pazdernik
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Lex C
authors.initials: LC
authors.lastname: Towns
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Snider
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sargentini
authors.affiliation: From the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri (Drs Snider, Sargentini, and Degenhardt); the departments of microbiology /immunology (Drs Singh and Sargentini), anatomy (Dr Towns), and osteopathic manipulative medicine (Dr Snider) at A.T. Still University-Kirksville College of Osteopathic Medicine in Missouri; and Research Support at A.T. Still University in Mesa, Arizona (Ms Pazdernik). Dr Ruhlen was affiliated with the A.T. Still Research Institute at A.T. Still University in Kirksville, Missouri, at the time of this study.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Degenhardt
mesh_terms: D000818:Animals; D016512:Ankle Injuries / Q000628:therapy; D015870:Gene Expression; D020869:Gene Expression Profiling; D006930:Hyperalgesia / Q000235:genetics* / Q000628:therapy; D007249:Inflammation / Q000235:genetics* / Q000628:therapy; D026301:Manipulation, Osteopathic; D046228:Microarray Analysis; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*
chemical_list: D012333:RNA, Messenger