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

Study Design. A lumbar radiculopathy model investigated-pain behavioral res ponses after nerve root reinjury. Objectives. To gain a further understanding of central sensitization and ne uroinflammation 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 lumba r root injury produces neuroimmunologic and neurochemical changes, sensitiz ing the spinal cord and causing pain responses to manifest with greater int ensity and longer duration after reinjury. However, this remains untested e xperimentally. Methods. Male Holtzman rats were divided into two groups: a sham group havi ng only nerve root exposure, and a chromic group in which the nerve root wa s ligated loosely with chromic gut suture. Animals underwent a second proce dure at 42 days. The chromic group was further divided into a reinjury grou p and a chromic-sham group, in which the lumbar roots were only re-exposed. Bilateral mechanical allodynia was continuously assessed throughout the st udy. Qualitative assessment of spinal cord glial activation and IL-beta exp ression was performed. Results. Mechanical allodynia was significantly greater on both the ipsilat eral and contralateral sides after reinjury (P < 0.001), and the response d id not return to baseline after reinjury, as it did with the initial injury . There were also persistent spinal astrocytic and microglial activation an d interleukin-1<beta> expression. Conclusions. The bilateral responses support central modulation of radicula r pain after nerve root injury. An exaggerated and more prolonged response bilaterally after reinjury suggests central sensitization after initial inj ury. Neuroinflammatory activation in the spinal cord further supports the h ypothesis that central neuroinflammation plays an important role in chronic radicular pain.