Quantification of neural tissue injury in a rat radiculopathy model: comparison of local deformation, behavioral outcomes, and spinal cytokine mRNA for two surgeons.
Clinical and experimental work indicate that a variety of factors contribute to radicular pain mechanisms, including mechanical injury. While it has been qualitatively suggested that the magnitude of nerve root mechanical injury affects the nature of the pain response, no study has quantified the local in vivo injury biomechanics in these models. Therefore, it was the purpose of this study to develop and implement an in vivo method to quantify compressive nerve root injury strain severity and characterize its effect on the resulting responses in an existing lumbar radiculopathy rat model. Male Holtzman rats were divided into a sham group with only nerve root exposure or a ligation group with the nerve root tightly ligated using silk suture. Using image analysis, nerve root radial strains were calculated at the time of injury for two surgeons. Mechanical allodynia was continuously assessed throughout the study and spinal cord cytokine mRNA levels were assayed on postoperative day 7. The degree of intersurgeon variability for imposing a ligation injury in this model was also assessed. Mean compressive injury strains in the nerve root were 32.8+/-14.2% and were not different for the two experimenters. Animals undergoing more severe ligation strains exhibited significantly heightened allodynia following injury and greater upregulation of the inflammatory cytokines IL-1alpha/beta, IL-6, and IL-10. Results indicate a direct correlation of local nerve root injury severity with the ensuing physiologic responses associated with nociception.
Winkelstein
B A
BA
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, HB 7125 One Medical Center Dr., Lebanon, NH 03756, USA. beth.a.winkelstein@darmouth.edu
Rutkowski
M D
MD
Weinstein
J N
JN
DeLeo
J A
JA
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D016207:Cytokines / Q000235:genetics*; D003714:Denervation / Q000009:adverse effects / Q000379:methods; D004185:Disability Evaluation; D004195:Disease Models, Animal; D007091:Image Processing, Computer-Assisted / Q000295:instrumentation / Q000379:methods; D008026:Ligation / Q000009:adverse effects / Q000379:methods; D008297:Male; D019635:Neurosurgical Procedures / Q000379:methods*; D009619:Nociceptors / Q000378:metabolism / Q000473:pathology; D015588:Observer Variation; D010146:Pain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D011843:Radiculopathy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000033:anatomy & histology / Q000502:physiology / Q000601:surgery*; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000293:injuries / Q000503:physiopathology / Q000601:surgery*; D016474:Weight-Bearing / Q000502:physiology
D016207:Cytokines; D012333:RNA, Messenger