Calcitonin Gene-Related Peptide (CGRP) as a Potential Therapeutic Target for Discogenic Back Pain.
Publication/Presentation Date
10-28-2026
Abstract
BACKGROUND CONTEXT: Discogenic back pain is a leading cause of disability worldwide, yet current treatments target symptoms rather than molecular mechanisms. Calcitonin gene-related peptide (CGRP), a neuropeptide involved in neurogenic inflammation, has been identified in intervertebral disc (IVD) tissue, but its impact on human disc cells is not well defined.
PURPOSE: Determine whether CGRP induces inflammatory cytokine and neurotrophic factor expression in human annulus fibrosus (AF) and nucleus pulposus (NP) cells, and whether monoclonal antibody via small-molecule blockade attenuates this response.
STUDY DESIGN: Basic laboratory study using human IVD cells cultured onto 3-D scaffolds METHODS: Primary AF and NP cells from surgical specimens were treated with recombinant human CGRP for one hour, with or without anti-CGRP antibodies (galcanezumab, erenumab) or small-molecule CGRP inhibitors. AF cells were exposed to inflammatory cytokines (TNF-α and IL-1β) and neurotrophic factors (BDNF and NGF). Expression of IL-6, TNF-α, BDNF and NGF were measured via quantitative PCR and analyzed using one-way ANOVA with mixed effects post hoc (P < 0.05 denotes statistical significance).
RESULTS: CGRP significantly increased IL-6 (2.79 fold, P < 0.001), BDNF (1.70 fold, P = .01) and NGF (1.61 fold, P < 0.001) expression in AF cells, while smaller effects occurred in NP cells. TNF-α and IL-1β significantly downregulated RAMP1 expression in AF cells but they significantly upregulated BDNF. Galcanezumab reduced IL-6 expression from 4.47-fold to 1.26-fold (P = 0.03 vs CGRP), and erenumab suppressed BDNF induction (P = 0.01). Anti-CGRP agents alone had no baseline effect.
CONCLUSION: CGRP induces inflammatory and neurotrophic signaling in human AF cells, attenuated by molecules that block CGRP.
CLINICAL SIGNIFICANCE: CGRP represents a promising molecular target for novel therapies addressing discogenic back pain.
ISSN
1878-1632
Published In/Presented At
Canseco, J. A., Markova, D., Ng, M. K., Chang, M., Eichbaum, Y., Banko, S. J., Dalton, J., Venkatesh, D., Karamian, B., Vaccaro, A. R., & Kepler, C. K. (2026). Calcitonin Gene-Related Peptide (CGRP) as a Potential Therapeutic Target for Discogenic Back Pain. The spine journal : official journal of the North American Spine Society, S1529-9430(26)00703-5. Advance online publication. https://doi.org/10.1016/j.spinee.2026.10.018
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
42951082
Department(s)
Administration and Leadership
Document Type
Article