Peripheral hypersensitivity to subthreshold stimuli persists after resolution of acute experimental disc-herniation neuropathy

Abstract

Objective: While acute disc-herniation radiculopathy frequently resolves without clinical sequelae, some patients experience long-term sensory or motor dysfunction. This study examined chronic sensitivity of the rodent hindpaw after resolution of an acute inflammatory neuropathy. Methods: C57BL/6 mice underwent mid-thigh sciatic nerve exposure, with sham animals exposed and experimental animals injured by placement of littermate tail nucleus pulposus (NP). Animals were evaluated for mechanical allodynia (Von Frey), thermal sensitivity (heat withdrawal and acetone latency), and gait stability (RotaRod), until the acute nociceptive phenotype resolved. Thereafter, animals were injected with intraplantar subthreshold capsaicin or vehicle followed by the same testing. At sacrifice, sciatic nerves were assessed for macrophage infiltration by immunohistochemistry, and dorsal root ganglion (DRG) explants were assessed for capsaicin sensitivity using cobalt staining. Results: NP-treated animals were allodynic after subthreshold capsaicin delivery compared with sham-operated controls and NP-treated animals delivered vehicle only. Early intraneural macrophage infiltration at one week dissipated by this three week timepoint. DRGs derived from NP-treated animals exhibited greater cobalt staining upon capsaicin exposure compared with shams. Conclusion: Non-compressive disc herniation creates long-term sensitization in the sciatic nerve distribution. This persists despite resolution of acute intraneural macrophage migration, and the demonstrated role of TRPV1 provides insight into the transformation of acute inflammatory pain into chronic neuropathic pain.