Date of this Version
The Journal of Pain, Vol. 24, iss. 4, Supplement, 49, April 2023. doi:10.1016/j.jpain.2023.02.150
Low back pain (LBP) is the leading cause of disability worldwide. Aberrant nerve growth into intervertebral discs is a common pathological feature of disc-associated LBP. Current treatments rely on short-term solutions using opioids or anti-inflammatory prescriptions which can lead to addiction and side effects, respectively. We hypothesize that removal of aberrant nerve fibers in the disc using nerve retraction compounds can alleviate discassociated LBP. We performed screening of nerve retraction compounds using adult rat dorsal root ganglia (DRG) explant culture in hydrogels to mimic disc innervation in vitro. Capsaicin, known to induce nerve retraction, was used as a positive control to screen for compounds with nerve retraction behavior (n=3 male, n=3 female rats). We identified two compounds (A and B) significantly reduced neurite length with minimal DRG cytotoxicity. We also assessed cytocompatibility with human disc cells in vitro (n=2 donors). Drug B significantly affects cell proliferation, but results from LIVE/DEAD staining and cell viability assay showed both compounds did not induce cell death but affects cellular metabolic activity. To test the in vivo safety of nerve retraction compounds, either 1X PBS (control), compound A or B was injected into L5/L6 disc of adult female rats (n=3 per group). No significant weight loss or behavioral changes (grimace, grooming, walking ability, gait, puffing) were observed up to 10 days postinjection. Overall, these data suggests that compounds A and B are safe, non-cytotoxic and potential nerve retraction agents for local denervation of innervated disc to alleviate disc-related LBP.
Funding by NSF CAREER1846857. NSF CAREER1846857.