Neuropathic Pain and Related Depression in Mice: The Effect of a Terpene and a Minor Cannabinoid in Combination

Authors

Jose Rios, The University of Texas Rio Grande ValleyFollow
Mohammed Alnoud, The University of Texas Rio Grande ValleyFollow
Mohammad Hussain, The University of Texas Rio Grande ValleyFollow
Zayd Ayas, The University of Texas Rio Grande ValleyFollow
Emmanuel Franco, The University of Texas Rio Grande ValleyFollow
Justin D. Mills, The University of Texas Rio Grande ValleyFollow
Joshua Nwose, The University of Texas Rio Grande ValleyFollow
Maria Sophia Malbas, The University of Texas Rio Grande ValleyFollow
Hiram L. Garcia, The University of Texas Rio Grande ValleyFollow
Manish Kumar Tripathi, The University of Texas Rio Grande ValleyFollow
Khalid Benamar, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

12-16-2025

Abstract

Background/Objectives: Neuropathic pain is one of the most severe types of chronic pain. Although it is difficult to manage, it often co-occurs with depression. Yet, no medication addresses the neuropathic pain and depression comorbidity. Therefore, developing integrated treatment strategies that address both pain and depression is a major public health priority and an unmet need affecting millions. Methods: In this study, we investigated the effect of combining a terpene, Beta-Caryophyllene (BCP), and cannabidiol (CBD) on neuropathic pain and associated depression. We employed a chronic constriction injury (CCI) neuropathic pain model and a series of behavioral tests to evaluate how oral administration of this combination influences neuropathic pain and depression-like behaviors in mice. We employed immunohistochemistry and proteomics approaches to explore the mechanism. Results: The analgesic effect of combining CBD and BCP is synergistic in neuropathic pain and also shows an antidepressant effect. Additionally, we found that this combination decreases neuroinflammation associated with CCI and affects specific genes involved in the inflammation. Conclusions: This work provides preclinical scientific evidence supporting the potential usefulness of this combination for neuropathic pain and associated depression.

Comments

© 2025 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Recommended Citation

Rios, J., Alnoud, M., Hussain, M. S., Ayas, Z., Franco, E., Mills, J., Nwose, J., Malbas, M. S., Garcia, H., Tripathi, M. K., & Benamar, K. (2025). Neuropathic Pain and Related Depression in Mice: The Effect of a Terpene and a Minor Cannabinoid in Combination. Biomedicines, 13(12), 3103. https://doi.org/10.3390/biomedicines13123103

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Publication Title

Biomedicines

DOI

10.3390/biomedicines13123103

Academic Level

faculty

Mentor/PI Department

Neuroscience