Changes in fractalkine and its receptor in the spinal cord obtained from rats with lumbar disc herniation

Abstract

Objetive: To investigate the chronic changes in the expression of the fractalkine and its receptor (CX3CR1) in the spinal cord, and pain-related behavior in a rat model of lumbar disc herniation. Method: Lumbar disc herniated rat model was made by implantation of autologous nucleus pulposus, harvested from between the second and third coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the dorsal root ganglion (DRG). Rats were tested for thermal hyperalgesia and mechanical allodynia of the plantar surface of both hindpaw on 2 days before surgery, and on 1, 5, 10, 20 and 30 days postoperatively (PO). Real time PCR and immunohistochemistry for fractalkine and its receptor on spinal dorsal horn and dorsal root ganglion were also done.. Results: Thermal hyperalgesia on both hindpaws was developed 5 days PO and mechanical allodynia in ipsilateral hindpaw 1 day PO, and these changes lasted throughout the observation period. The mRNA expression of fractalkine and its receptor in the dorsal horn was upregulated from 5 days PO and maintained throughout more than 30 days PO. Similarly, the expression of fractalkine and its receptor were also upregulated in DRG. In immunohistochemical study, increased expression of fractalkine in neurons and astrocytes in ipsilateral dorsal horn was observed. The expression of fractalkine receptor in microglia was also increased in the dorsal horn ipsilateral to disc herniation. Conclusion: Our results demonstrate that lumbar disc herniation with nucleus pulposus induces thermal hyperalgesia and mechanical allodynia, and upregulates the expression of fractalkine and its receptor in ipsilateral spinal neurons and glial cells and DRG. Fractalkine and its receptor may be a pivotal chemokine in development and maintenance of radicular pain state. Acknowledgements: This work was supported by grant No. 205-B-000-042 by the Basic Research Program of the Korea Science & Engineering Foundation.