Introduction: While acute disc-herniation induced radiculopathy most frequently resolves without clinical sequelae, a fraction of patients experience long-term sensory dysfunction. This study examined chronic sensitivity of the rodent hindpaw following resolution of acute inflammatory neuropathy.
Methods: C57BL/6 mice underwent mid-thigh sciatic nerve dissection, with either exposure only (control) or placement of nucleus pulposus (NP). Animals were evaluated throughout one, three, and five weeks for mechanical allodynia, thermal hyperalgesia, cold allodynia, and gait stability. At each time point, animals received intraplantar injection of capsaicin (0.1µg) or vehicle alone, thereafter the same behavioral testing. Immunohistochemistry was performed of sciatic nerve, dorsal root ganglion (DRG), and spinal cord for inflammatory activation as well as TRPV1 receptor expression. Ex vivo DRG explants were assessed for capsaicin sensitivity to TRPV1 activation (cobalt staining).
Results: Upon resolution of acute inflammatory pain, mice at three and five weeks (but not one week) demonstrated profound mechanical allodynia to subthreshold capsaicin compared with sham-operated controls or NP-stimulation animals delivered vehicle only. Conversely, perineural lymphocyte and intraneural macrophage infiltration was only observed at one week. Heightened spinal cord dorsal horn and DRG TRPV1 expression were seen, and DRG explants derived from NP-treated animals exhibited greater cobalt staining upon capsaicin stimulation compared with controls.
Conclusions: Non-compressive disc herniation sensitizes the sciatic nerve distribution in this animal model, despite resolution of acute intraneural macrophage migration. The demonstrated role of TRPV1 may explain how acute inflammatory pain transforms into chronic neuropathic pain. Decreasing TRPV1 expression may prevent the development of the long-term painful phenotype.
Patient Care: Understanding how long-term sensitization occurs after acute inflammatory radiculopathy will help define populations at risk of developing neuropathic pain and identify mechanisms by which that transition can be prevented.
Learning Objectives: 1) Understand the transition of acute inflammatory pain to chronic neuropathic pain in the pathophysiology of non-compressive disc herniation radiculopathy.
2) Identify molecular targets to decrease the incidence of neuropathic pain after disc herniation radiculopathy.
References: Sinclair SM, Shamji MF, Chen J, Jing L, Richardson WJ, Brown CR, Fitch RD, Setton LA. Attenuation of Inflammatory Events in Human Intervertebral Disc Cells with a Tumor Necrosis Factor Antagonist. Spine, 2011. 36(15):1190-6
Shamji MF, Allen KD, So S, Jing L, Adams SB, Schuh R, Huebner J, Kraus VB, Friedman AH, Setton LA, Richardson WJ. Gait Abnormalities and Inflammatory Cytokines in an Autologous Nucleus Pulposus Model of Radiculopathy. Spine, 2009. 34(7):648-54