Introduction: Cervical disc disease and radiculopathy are common, affecting 14-50% of the adult population [1,2]. Nerve root compression induces axonal damage and spinal inflammation that lead behavioral sensitivity [3]. Little is known about the integrated neuronal responses in the spinal cord and thalamus due to painful radicular insults. As such, this study determined if neuronal hypersensitivity in these regions of the central nervous system persists after a painful radicular injury.

Methods: Male Holtzman rats underwent either a painful transient C7 nerve root compression (n=6) or sham surgery (n=5). Behavioral sensitivity was assessed for 14 days by measuring the number of paw withdrawals elicited by stimulation using a series of von Frey filaments (1.4g, 2.0g, 4.0g) [4,5]. On day 14, evoked neuronal recordings were made from the contralateral ventral posteriolateral nucleus of the thalamus (n=38 neurons/injury; n=19 neurons/sham) and the ipsilateral spinal dorsal horn (n=11 neurons/injury; n=14 neurons/sham) during stimulation of the forepaw by non-noxious (1.4g, 4.0g) and noxious (10.0g, 26.0g) filaments [4,5]. Behavioral and evoked spike data were compared between groups using t-tests.

Results: The number of paw withdrawals increased significantly (p<0.049) after root compression for all filaments (Figure 1). At day 14 after painful injury, the evoked spikes in the thalamus also increased significantly (p<0.043) over sham for all stimuli (Figure 1). Similarly, spinal neuronal activity increased significantly (p<0.019) after injury for all von Frey filaments except 1.4g. (Figure 1).

Conclusions: A transient nerve root compression induces mechanical sensitivity that is maintained for up to 2 weeks, associated with parallel sustained neuronal hypersensitivity throughout the nervous system, in both the local spinal level of injury and the thalamic relay nuclei involved in the sensation of pain. These findings support the hypothesis that sustained electrophysiological modifications occur in radiculopathy and that central sensitization contributes to painful radiculopathy.

Patient Care: The results of this research provides insight into the neuronal physiology of radicular pain in the central nervous system. This information can be used to identify novel targets for treatment of chronic radicular pain via neuromodulation or by the use of drugs that take into consideration this physiology.

Learning Objectives: By the conclusion of this session participants should be able to: 1) Discuss neuronal responses to painful radiculopathy in the central nervous system and 2) Identify the areas of the central nervous system that are modulated in persistent pain states.

References: 1. Côté P, Cassidy JD, Carroll LJ, Kristman V. The annual incidence and course of neck pain in the general population: a population-based cohort study. Pain. 2004 Dec;112(3):267-73. 2. Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, et al. The burden and determinants of neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine. 2008 Feb 15;33(4 Suppl):S39-51 3. Nicholson KJ, Guarino BB, Winkelstein BA. Transient nerve root compression load and duration differentially mediate behavioral sensitivity and associated spinal astrocyte activation and mGLuR5 expression. Neuroscience. 2012 May 3;209:187-95. 4. Quinn KP, Dong L, Golder FJ, Winkelstein BA. Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. Pain. 2010 Nov;151(2):414-21 5. Hubbard RD, Winkelstein BA. Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine. 2005 Sep 1;30(17):1924-32.