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Sustained Neuronal Hyperexcitability Is Evident in the Thalamus After a Transient Cervical Radicular Injury

Syré, Peter P. MD*; Weisshaar, Christine L. MS*,†; Winkelstein, Beth A. PhD*,†

doi: 10.1097/BRS.0000000000000392
Basic Science

Study Design. This study used extracellular electrophysiology to examine neuronal hyperexcitability in the ventroposterolateral nucleus (VPL) of the thalamus in a rat model of painful radiculopathy.

Objective. The goal of this study was to quantify evoked neuronal excitability in the VPL at day 14 after a cervical nerve root compression to determine thalamic processing of persistent radicular pain.

Summary of Background Data. Nerve root compression often leads to radicular pain. Chronic pain is thought to induce structural and biochemical changes in the brain affecting supraspinal signaling. In particular, the VPL of the thalamus has been implicated in chronic pain states.

Methods. Rats underwent a painful transient C7 nerve root compression or sham procedure. Ipsilateral forepaw mechanical allodynia was assessed on days 1, 3, 5, 7, 10, and 14 and evoked thalamic neuronal recordings were collected at day 14 from the contralateral VPL, whereas the injured forepaw was stimulated using a range of non-noxious and noxious mechanical stimuli. Neurons were classified on the basis of their response to stimulation.

Results. Behavioral sensitivity was elevated after nerve root compression starting at day 3 and persisted until day 14 (P < 0.049). Thalamic recordings at day 14 demonstrated increased neuronal hyperexcitability after injury for all mechanical stimuli (P < 0.024). In particular, wide dynamic range neurons demonstrated significantly more firing after injury compared with sham in response to von Frey stimulation (P < 0.0001). Firing in low threshold mechanoreceptive neurons was not different between groups.

Conclusion. These data demonstrate that persistent radicular pain is associated with sustained neuronal hyperexcitability in the contralateral VPL of the thalamus. These findings suggest that thalamic processing is altered during radiculopathy and these changes in neuronal firing are associated with behavioral sensitivity.

Level of Evidence: N/A

A painful, transient nerve root compression was applied in a rat model, with assessment of mechanical allodynia until electrophysiology recordings in the thalamus on day 14. Mechanical allodynia and thalamic neuronal firing increase after radicular injury, indicating sustained thalamic activity after a transient radicular insult producing persistent behavioral sensitivity.

From the Departments of *Neurosurgery and

Bioengineering, University of Pennsylvania, Philadelphia.

Address correspondence and reprint requests to Beth A. Winkelstein, PhD, Department of Bioengineering, 240 Skirkanich Hall, 210 S 33rd St, Philadelphia, PA 19104; E-mail:

Acknowledgment date: January 18, 2014. First revision date: March 1, 2014. Second revision date: March 15, 2014. Acceptance date: April 8, 2014.

The manuscript submitted does not contain information about medical device(s)/drug(s).

Catherine Sharpe Foundation and T32 Brain Injury Training (grant NS043126) fellowship funds were received in support of this work.

No relevant financial activities outside the submitted work.

© 2014 by Lippincott Williams & Wilkins