Nerve root injury severity differentially modulates spinal glial activation in a rat lumbar radiculopathy model: considerations for persistent pain.
Nerve root deformation magnitude affects behavioral sensitivity and spinal cytokine expression in a lumbar radiculopathy model. Despite evidence suggesting spinal glia play a role in persistent pain, no study has examined the relationship between injury severity in painful radiculopathy and spinal glial activation. This study quantified local in vivo biomechanics for nerve root injury, describing effects on temporal glial activation. Sham rats had only nerve root exposure; ligation rats received a tight L5 nerve root ligation with silk suture. Using image analysis, the magnitude of nerve root compressive strain was calculated at the time of injury. Mechanical allodynia was assessed from days 1 to 14 following injury and spinal microglial and astrocytic expression were evaluated using immunohistochemistry on days 1, 3, 7, and 14. More severe ligations produced greater microglial activation, indicating injury severity modulates spinal microglial activation. However, astrocytic activation levels did not demonstrate any relationship with the degree of initial injury severity. While allodynia decreased slightly over time following injury, the temporal changes in mechanical allodynia were not significant. Microglial activation levels were maintained temporally, and in some cases increased over time; whereas, changes in astrocytic activation levels were not temporally or injury-related. While initial nerve root injury severity likely modulates spinal OX-42 (CR3/CD11b) expression, OX-42 staining does not directly correlate with nerve root injury-induced mechanical allodynia.
Winkelstein
Beth A
BA
Department of Anesthesiology, Dartmouth, Hitchcock Medical Center, Lebanon, NH 03756, USA. winkelst@seas.upenn.edu
DeLeo
Joyce A
JA
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D015601:Injury Severity Score; D008161:Lumbosacral Region; D008297:Male; D017628:Microglia / Q000378:metabolism*; D010146:Pain / Q000378:metabolism*; D011843:Radiculopathy / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013126:Spinal Nerve Roots / Q000293:injuries*; D013997:Time Factors