Repeated injury to the lumbar nerve roots produces enhanced mechanical allodynia and persistent spinal neuroinflammation

Study Design. A lumbar radiculopathy model investigated-pain behavioral responses after nerve root reinjury. Objectives. To gain a further understanding of central sensitization and neuroinflammation associated with chronic lumbar radiculopathy after repeated nerve root injury. Summary of Background Data. The pathophysiologic mechanisms associated with chronic radicular pain remain obscure. It has been hypothesized that lumbar root injury produces neuroimmunologic and neurochemical changes, sensitizing the spinal cord and causing pain responses to manifest with greater intensity and longer duration after reinjury. However, this remains untested experimentally. Methods. Male Holtzman rats were divided into two groups: a sham group having only nerve root exposure, and a chromic group in which the nerve root was ligated loosely with chromic gut suture. Animals underwent a second procedure at 42 days. The chromic group was further divided into a reinjury group and a chromic-sham group, in which the lumbar roots were only re-exposed. Bilateral mechanical allodynia was continuously assessed throughout the study. Qualitative assessment of spinal cord glial activation and IL-beta expression was performed. Results. Mechanical allodynia was significantly greater on both the ipsilateral and contralateral sides after reinjury (P < 0.001), and the response did not return to baseline after reinjury, as it did with the initial injury. There were also persistent spinal astrocytic and microglial activation and interleukin-1<beta> expression. Conclusions. The bilateral responses support central modulation of radicular pain after nerve root injury. An exaggerated and more prolonged response bilaterally after reinjury suggests central sensitization after initial injury. Neuroinflammatory activation in the spinal cord further supports the hypothesis that central neuroinflammation plays an important role in chronic radicular pain.