Neuronal hyperexcitability in the dorsal horn after painful facet joint injury
Kyle P Quinn, Ling Dong, Francis J Golder, Beth A Winkelstein, Kyle P Quinn, Ling Dong, Francis J Golder, Beth A Winkelstein
Abstract
Excessive cervical facet capsular ligament stretch has been implicated as a cause of whiplash-associated disorders following rear-end impacts, but the pathophysiological mechanisms that produce chronic pain in these cases remain unclear. Using a rat model of C6-C7 cervical facet joint capsule stretch that produces sustained mechanical hyperalgesia, the presence of neuronal hyperexcitability was characterized 7 days after joint loading. Extracellular recordings of spinal dorsal horn neuronal activity between C6 and C8 (117 neurons) were obtained from anesthetized rats, with both painful and non-painful behavioral outcomes established by the magnitude of capsule stretch. The frequency of neuronal firing during noxious pinch (p<0.0182) and von Frey filaments applications (4-26g) to the forepaw was increased (p<0.0156) in the painful group compared to the non-painful and sham groups. In addition, the incidence and frequency of spontaneous and after discharge firing were greater in the painful group (p<0.0307) relative to sham. The proportion of cells in the deep laminae that responded as wide dynamic range neurons also was increased in the painful group relative to non-painful or sham groups (p<0.0348). These findings suggest that excessive facet capsule stretch, while not producing visible tearing, can produce functional plasticity of dorsal horn neuronal activity. The increase in neuronal firing across a range of stimulus magnitudes observed at day 7 post-injury provides the first direct evidence of neuronal modulation in the spinal cord following facet joint loading, and suggests that facet-mediated chronic pain following whiplash injury is driven, at least in part, by central sensitization.
Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Figures
![Figure 1. Forepaw stimulation protocol](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f1.jpg)
![Figure 2. Representative extracellular recordings during the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f2.jpg)
![Figure 3. Neuronal hyperexcitability in the dorsal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f3.jpg)
![Figure 4. Evoked neuronal firing increases with…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f4.jpg)
Figure 5. The average number of spikes…
Figure 5. The average number of spikes evoked during von Frey filament stimulation of the…
Figure 6. Afterdischarge rates increase after painful…
Figure 6. Afterdischarge rates increase after painful facet injury in response to von Frey filament…
- Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury.Crosby ND, Weisshaar CL, Winkelstein BA. Crosby ND, et al. Neurosci Lett. 2013 May 10;542:102-6. doi: 10.1016/j.neulet.2013.03.019. Epub 2013 Mar 21. Neurosci Lett. 2013. PMID: 23523644 Free PMC article.
- An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension.Winkelstein BA, Santos DG. Winkelstein BA, et al. Spine (Phila Pa 1976). 2008 Apr 15;33(8):856-62. doi: 10.1097/BRS.0b013e31816b4710. Spine (Phila Pa 1976). 2008. PMID: 18404104
- Gabapentin alleviates facet-mediated pain in the rat through reduced neuronal hyperexcitability and astrocytic activation in the spinal cord.Dong L, Crosby ND, Winkelstein BA. Dong L, et al. J Pain. 2013 Dec;14(12):1564-72. doi: 10.1016/j.jpain.2013.07.016. Epub 2013 Oct 4. J Pain. 2013. PMID: 24094695 Free PMC article.
- Painful Cervical Facet Joint Injury Is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Differentially Relate to Local Tissue Injury Severity.Ita ME, Crosby ND, Bulka BA, Winkelstein BA. Ita ME, et al. Spine (Phila Pa 1976). 2017 Jun 15;42(12):E695-E701. doi: 10.1097/BRS.0000000000001934. Spine (Phila Pa 1976). 2017. PMID: 27755498 Free PMC article.
- Pain generation in lumbar and cervical facet joints.Cavanaugh JM, Lu Y, Chen C, Kallakuri S. Cavanaugh JM, et al. J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:63-7. doi: 10.2106/JBJS.E.01411. J Bone Joint Surg Am. 2006. PMID: 16595446 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Action Potentials / physiology
- Animals
- Cervical Vertebrae
- Disease Models, Animal
- Hyperalgesia / etiology
- Hyperalgesia / pathology*
- Male
- Pain Measurement / methods
- Pain Threshold / physiology
- Physical Stimulation / adverse effects
- Posterior Horn Cells / physiology*
- Psychophysics / methods
- Rats
- Rats, Sprague-Dawley
- Spinal Cord / pathology*
- Zygapophyseal Joint / injuries
- Zygapophyseal Joint / physiopathology*
- Full Text Sources
- Medical
- Miscellaneous
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![Figure 5. The average number of spikes…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f5.jpg)
Figure 6. Afterdischarge rates increase after painful…
Figure 6. Afterdischarge rates increase after painful facet injury in response to von Frey filament…
- Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury.Crosby ND, Weisshaar CL, Winkelstein BA. Crosby ND, et al. Neurosci Lett. 2013 May 10;542:102-6. doi: 10.1016/j.neulet.2013.03.019. Epub 2013 Mar 21. Neurosci Lett. 2013. PMID: 23523644 Free PMC article.
- An intact facet capsular ligament modulates behavioral sensitivity and spinal glial activation produced by cervical facet joint tension.Winkelstein BA, Santos DG. Winkelstein BA, et al. Spine (Phila Pa 1976). 2008 Apr 15;33(8):856-62. doi: 10.1097/BRS.0b013e31816b4710. Spine (Phila Pa 1976). 2008. PMID: 18404104
- Gabapentin alleviates facet-mediated pain in the rat through reduced neuronal hyperexcitability and astrocytic activation in the spinal cord.Dong L, Crosby ND, Winkelstein BA. Dong L, et al. J Pain. 2013 Dec;14(12):1564-72. doi: 10.1016/j.jpain.2013.07.016. Epub 2013 Oct 4. J Pain. 2013. PMID: 24094695 Free PMC article.
- Painful Cervical Facet Joint Injury Is Accompanied by Changes in the Number of Excitatory and Inhibitory Synapses in the Superficial Dorsal Horn That Differentially Relate to Local Tissue Injury Severity.Ita ME, Crosby ND, Bulka BA, Winkelstein BA. Ita ME, et al. Spine (Phila Pa 1976). 2017 Jun 15;42(12):E695-E701. doi: 10.1097/BRS.0000000000001934. Spine (Phila Pa 1976). 2017. PMID: 27755498 Free PMC article.
- Pain generation in lumbar and cervical facet joints.Cavanaugh JM, Lu Y, Chen C, Kallakuri S. Cavanaugh JM, et al. J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:63-7. doi: 10.2106/JBJS.E.01411. J Bone Joint Surg Am. 2006. PMID: 16595446 Review.
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Action Potentials / physiology
- Animals
- Cervical Vertebrae
- Disease Models, Animal
- Hyperalgesia / etiology
- Hyperalgesia / pathology*
- Male
- Pain Measurement / methods
- Pain Threshold / physiology
- Physical Stimulation / adverse effects
- Posterior Horn Cells / physiology*
- Psychophysics / methods
- Rats
- Rats, Sprague-Dawley
- Spinal Cord / pathology*
- Zygapophyseal Joint / injuries
- Zygapophyseal Joint / physiopathology*
- Full Text Sources
- Medical
- Miscellaneous
![Figure 6. Afterdischarge rates increase after painful…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2955815/bin/nihms228409f6.jpg)
Source: PubMed