Author ORCID Identifier
Date Available
8-9-2027
Year of Publication
2025
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Pharmacy
Department/School/Program
Pharmaceutical Sciences
Faculty
Chang-Guo Zhan
Faculty
Feola David
Faculty
Gonzalez Duque, Octavio A.
Abstract
Postoperative pain presents a significant clinical challenge, as inadequate management can delay functional recovery, prolong hospital stays, and increase the risk of transitioning to chronic pain. While opioid analgesics are the gold standard for treatment of severe acute postoperative pain, they are associated with serious adverse effects, including respiratory depression, physical dependency, and opioid-induced hyperalgesia, a key contributor to chronic postoperative pain. Lapatinib, a tyrosine kinase inhibitor originally developed as an anticancer agent, has demonstrated analgesic potential in both preclinical and clinical settings. These findings suggest that lapatinib may be a promising candidate for repurposing as a novel pain management therapy. Notably, lapatinib does not appear to engage the brain's reward pathways, thereby minimizing the risk of physical dependence, a major limitation of current opioid-based treatments. While its efficacy has been explored in several models of chronic pain, there is currently no evidence supporting its use in managing severe acute postoperative pain or the associated inflammatory response. In this study, we demonstrated Lapatinib's anti-inflammatory effects in vitro using RAW 264.7 cells, where it significantly reduced prostaglandin E2 (PGE2) production and suppressed proinflammatory cytokines following lipopolysaccharide (LPS) treatment. In a mouse model of postoperative pain, preoperative Lapatinib administration alleviated both allodynia and hyperalgesia. This effect was accompanied by suppression of proinflammatory cytokines and upregulation of IL-10 in injured paw tissue. Our findings suggest that Lapatinib holds promise as a novel analgesic for postoperative pain, with potential advantages over current treatments due to its targeted action and reduced adverse effect profile. Further investigation is warranted to explore its clinical applicability in pain management.
Digital Object Identifier (DOI)
https://doi.org/10.13023/etd.2025.370
Funding Information
This study was supported by the United States Department of Defense investigator-initiated award Grant (no.: W81XWH2211000) in 2018
Recommended Citation
Kyomuhangi, Annet, "INVESTIGATION OF LAPATINIB AS A NOVEL THERAPEUTIC FOR POSTOPERATIVE PAIN MANAGEMENT" (2025). Theses and Dissertations--Pharmacy. 170.
https://uknowledge.uky.edu/pharmacy_etds/170
