Affiliation:
1. Department of Neurosurgery, Fuzhou 900th Hospital, Fuzong Clinical Medical College of Fujian Medical University
2. Department of Neurosurgery, Xiang'an Hospital affiliated to Xiamen University
Abstract
Abstract
Background
Patients with spinal cord injury (SCI) often present with different degrees of neuropathic pain (NP). Glia-mediated inflammatory response plays a key role. The transient receptor potential vanilloid subtype 1 (TRPV1), as an ion channel receptor closely related to pain, plays an important role in NP, although its mechanism remains unclear. We explored the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of C-X3-C motif chemokine ligand 1 (CX3CL1)-positive glial cells.
Methods
The SCI rat model was established using the modified Allen’s spinal cord injury model. After SCI, rats in each group were administered the TRPV1 antagonist SB705498 (10 mg/kg) or 2 mL of vehicle intragastrically for 7 consecutive days. The hindlimb motor function of rats after injury was assessed by the Basso, Beattie, and Bresnahan rating scale; Von Frey fibres and plantar thermal stimulation were used to evaluate the changes in rats’ mechanical paw withdrawal threshold (PWT) and thermal paw withdrawal latency (PWL), respectively; haematoxylin and eosin staining, double immunofluorescent staining, and Western blotting were used to investigate the role of TRPV1 in NP after SCI and its effect on the proliferation and activation of CX3CL1-positive glial cells.
Results
The chemokine CX3CL1 was mainly expressed in the dorsal horn neurons of the spinal cord and also to a certain extent in microglia, astrocytes, and oligodendrocytes after SCI. The expression of TRPV1 and CX3CL1 in the dorsal horn of the spinal cord in rats was significantly upregulated, and the PWT and PWL of rats were significantly decreased after SCI. The TRPV1 antagonist not only inhibited the activation of TRPV1, but also significantly inhibited the apoptosis of neurons and oligodendrocytes and proliferation and activation of inflammation-related CX3CL1-positive glial cells induced by SCI.
Conclusion
These results suggest that TRPV1 is involved in the occurrence and development of NP after SCI in rats by mediating the proliferation and activation of CX3CL1-positive glial cells in the dorsal horn of the spinal cord; inhibition of TRPV1 activity attenuates the proliferation and activation of CX3CL1-positive glial cells, thereby reducing symptoms of central sensitisation.
Publisher
Research Square Platform LLC
Reference51 articles.
1. Comparative transcriptomics of rat and axolotl after spinal cord injury dissects differences and similarities in inflammatory and matrix remodeling gene expression patterns;Tica J;Front Neurosci,2018
2. Spinal cord injury: pathophysiology, multimolecular interactions, and underlying recovery mechanisms;Anjum A;Int J Mol Sci,2020
3. Neurological recovery following traumatic spinal cord injury: A systematic review and meta-analysis;Khorasanizadeh M;J Neurosurg,2019
4. National Spinal Cord Injury Statistical Center. National spinal cord injury statistical center. Birmingham, AL: Facts and Figures at a Glance. University of Alabama at Birmingham; 2016.
5. Spinal cord injury pain;Attal N;Rev Neurol,2021