title: Lumbar nerve root injury induces central nervous system neuroimmune activation and neuroinflammation in the rat: relationship to painful radiculopathy.
abstract: METHODS
  These studies were designed to examine the role of central neuroimmune activation and neuroinflammation in a rat model of lumbar radiculopathy.
  
  
  OBJECTIVE
  In the present study the authors investigated the role of neuroimmune activation using immunocytochemistry to detect expression of major histocompatibility complex Class II, cluster determinant 4, intracellular adhesion molecule-1 (ICAM-1), and platelet endothelial cellular adhesion molecule-1 (PECAM-1). The role of central neuroinflammation was investigated using radiation bone marrow chimeric rats.
  
  
  BACKGROUND
  The pathologic mechanisms resulting in painful lumbar radiculopathy secondary to nerve root injury remain obscure. There is a growing body of evidence that central neuroimmune activation and neuroinflammation may play a key role in the initiation and maintenance of various pain states, including lumbar radiculopathy.
  
  
  METHODS
  Male Holtzman rats undergoing mechanical sensitivity testing were divided into two groups: a sham group and a chromic gut suture group. Animals were killed on day 14 post surgery. Male Holtzman rats, used to detect cluster determinant 4, major histocompatibility complex Class II, and CAM spinal expression, were divided into three groups: a normal group, a sham surgery group, and a chromic group. The male Brown Norway rats used to make the radiation bone marrow chimeras were divided into two groups: a sham group and a chromic group. Animals were killed at 1, 3, 7 or 14 days following surgery.
  
  
  RESULTS
  Nerve root injury in the rat produced increased spinal major histocompatibility complex Class II, cluster determinant 4, ICAM-1, and PECAM-1 immunoreactivity and increased bilateral sensitivity to tactile stimuli. Leukocyte trafficking into the spinal parenchyma was observed, which increased over time after nerve root injury.
  
  
  CONCLUSIONS
  The presence of bilateral mechanical allodynia and spinal neuroimmune changes following nerve root injury supports the hypothesis that central sensitization through activation of immune mediators, coupled with macrophage traffic across the blood-brain barrier, plays a key role in the development and maintenance of radicular pain.
authors.affiliation: Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
authors.forename: Maria D
authors.initials: MD
authors.lastname: Rutkowski
authors.forename: Beth A
authors.initials: BA
authors.lastname: Winkelstein
authors.forename: William F
authors.initials: WF
authors.lastname: Hickey
authors.forename: Janice L
authors.initials: JL
authors.lastname: Pahl
authors.forename: Joyce A
authors.initials: JA
authors.lastname: DeLeo
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000096:biosynthesis; D002452:Cell Count; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D017116:Low Back Pain / Q000209:etiology; D008161:Lumbosacral Region; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology; D009443:Neuritis / Q000209:etiology* / Q000473:pathology; D015213:Neuroimmunomodulation / Q000276:immunology; D010147:Pain Measurement; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D011828:Radiation Chimera; D011843:Radiculopathy / Q000150:complications* / Q000503:physiopathology; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000293:injuries / Q000503:physiopathology*
chemical_list: D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1