Lapatinib Suppressed the Expression of Proinflammatory Cytokines and Alleviated Pain Behavior in a Mouse Model of Postoperative Pain

Postoperative pain remains a major clinical challenge, as inadequate management can delay functional recovery, prolong hospitalization, and increase the risk of chronic pain development. Opioid analgesics, while considered the gold standard for treating severe acute postoperative pain, are limited by adverse effects such as respiratory depression, dependence, and opioid-induced hyperalgesia, the latter being a key driver of persistent postoperative pain. Lapatinib, originally developed as an anticancer therapy, has recently shown analgesic potential in both preclinical and clinical studies. Importantly, unlike opioids, lapatinib does not appear to activate central reward pathways, thereby minimizing the risk of dependence. Although its efficacy has been investigated in several chronic pain models, its role in acute postoperative pain and the associated inflammatory response has not been explored. In this study, we demonstrated that lapatinib exerts anti-inflammatory effects in vitro by suppressing proinflammatory mediators (TNF, IL-1{beta}, IL-6, COX-2, MMP, chemokines, mPGES-1 and PGE2) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. In a mouse model of postoperative pain, preoperative administration of lapatinib attenuated both mechanical allodynia and thermal hyperalgesia. These behavioral effects were accompanied by decreased proinflammatory mediator expression (TNF, IL-1{beta}, IL-6, COX-2, and mPGES-1) and increased IL-10 levels in the injured paw tissue. Our findings highlight lapatinib as a promising candidate for repurposing as a novel analgesic for postoperative pain. Its targeted mechanism of action and lower potential for adverse effects compared with opioids support further investigation into its clinical utility in pain management. Significant StatementWe found that lapatinib, a cancer drug with no risk of dependence, reduces inflammation and alleviates pain in a mouse model of postoperative pain. These findings suggest lapatinib could be repurposed as a safer, non-opioid therapy for surgical pain management. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/698212v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@d62c5corg.highwire.dtl.DTLVardef@fa84ddorg.highwire.dtl.DTLVardef@128e143org.highwire.dtl.DTLVardef@dd1720_HPS_FORMAT_FIGEXP M_FIG C_FIG