Inhibiting Brain-Derived Neurotrophic Factor (Bdnf) at the Punctured Intervertebral Disk Downregulates Pain-Related Neuropeptide Production in Dorsal Root Ganglia in Rats

Abstract

Introduction BDNF-a neurotrophin in dorsal root ganglion (DRG) neurons-is known to be anterogradely transported to the spinal cord and transmits pain signals existing in the central nervous system. A previous study has recently reported its presence in the peripheral sites of degenerative IVDs, although its association with discogenic pain remains unclear. The present study aimed to investigate the association between BDNF and pain-related sensory innervation of multiple-punctured lumbar IVD in rats. Materials and Methods Forty female Sprague-Dawley rats were equally divided into four groups: naïve, sham, and two agent-treated groups (vehicle (saline-treated) and anti-BDNF (anti-BDNF antibody) group). L5-6 IVDs of the agent-treated rats were exposed and injured by repeated punctures. The retrograde neurotracer Fluoro-Gold (FG) and treatment agents were intradiscally applied. In the sham group, FG alone was applied onto uninjured IVD. One week later, L1-3 DRGs were harvested and immunolabeled for the inflammatory pain-related calcitonin gene-related peptide (CGRP), that is, the pain marker. The proportions of FG-labeled CGRP-immunoreactive (-ir) DRG neurons were assessed. BDNF concentration of each L5-6 IVD was measured using enzyme-linked immunosorbent assay (ELISA). Results FG-labeled DRG neurons were almost equally prevalent at each DRG level. The proportions of FG-labeled CGRP-ir DRG neurons in the two agent-treated groups were significantly elevated ( p < 0.05) compared with the naïve and sham groups and were significantly decreased in the anti-BDNF group as compared to the vehicle group ( p < 0.05). BDNF concentrations were elevated maximally in the vehicle group but suppressed in the anti-BDNF group. Conclusion Direct intradiscal application of the anti-BDNF antibody significantly suppressed both CGRP production and the local concentration of BDNF. Our results indicate a possible association between the local production of BDNF and the pathophysiology of discogenic pain. I confirm having declared any potential conflict of interest for all authors listed on this abstract Yes Disclosure of Interest None declared