| Title |
Neuropathic pain in a chronic CNS injury model is mediated by corticospinal-targeted spinal interneurons |
| Authors |
Guan,Xiaofei;Burke Neurological Institute;ORCID:0000-0002-3675-4344
Zhu,Yanjie;Burke Neurological Institute
Zhong,Jian;Burke Neurological Institute;ORCID:0000-0003-2031-232X
Hollis,Edmund;Burke Neurological Institute;ORCID:0000-0002-4535-4668
|
| Description |
Chronic neuropathic pain is a persistent and debilitating outcome of traumatic central nervous system injury, affecting up to 80% of individuals with chronic injury. Post-injury pain is refractory to clinical treatments due to the limited understanding of the brain-spinal cord circuits that underlie pain signal processing. The corticospinal tract (CST) plays critical roles in sensory modulation during skilled movements and tactile sensation; however, a direct role for the CST in injury-associated neuropathic pain is unclear. Here we show that complete, selective CST transection at the medullary pyramids leads to hyperexcitability within lumbar deep dorsal horn and hindlimb allodynia in chronically injured adult mice. Chemogenetic regulation of CST-targeted lumbar spinal interneurons demonstrates that dysregulation of activity in this circuit underlies the development of tactile allodynia in chronic injury. Our findings shed light on an unrecognized circuit mechanism implicated in CNS injury-induced neuropathic pain and provide a novel target for therapeutic intervention.
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| License |
Creative Commons CC0 1.0 Public Domain Dedication (https://creativecommons.org/publicdomain/zero/1.0/)
|
| References |
Guan X, Zhu Y, Zhong J, and Hollis E (2024) Neuropathic pain in a chronic CNS injury model is mediated by corticospinal-targeted spinal interneurons. doi: https://doi.org/10.1101/2024.04.11.589134 [doi.org/10.1101/2024.04.11.589134] (IsSupplementTo)
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| Funding |
Craig H. Neilsen Foundation, 998694
NYS DoH, C30844GG
National Institutes of Health, R01 NS099568
National Institutes of Health, DP2 NS106663
National Institutes of Health, R01 NS105725
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| Keywords |
Neuropathic pain
Spinal cord injury
Sensory modulation
Tactile allodynia
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| Resource Type |
Dataset
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