Curcumin attenuates uterine pain in mice through suppression of neuroinflammation in the DRG and spinal cord.

Abstract

Uterine pain associated with labor, dysmenorrhea, or endometriosis is often driven by inflammation, which enhances nociceptive signaling and contributes to hyperalgesia. Although nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids are commonly prescribed, their clinical application is limited by side effects, and a subset of patients exhibit inadequate or no response to NSAID therapy. Curcumin, a natural polyphenol extracted from Curcuma longa, exhibits well-documented anti-inflammatory and analgesic properties. In this study, we investigated the analgesic efficacy and underlying mechanisms of curcumin in a mouse model of uterine pain. Both intraperitoneal and intrathecal administration of curcumin significantly reduced writhing responses and improved locomotor performance in open-field tests. Molecular analyses revealed that estrogen and oxytocin treatment induced activation of glial cells in the dorsal root ganglia (DRG) and spinal cord. Intrathecal curcumin attenuated the activation of satellite glial cells and macrophages in the DRG, suppressed MAPK signaling (ERK, JNK, and p38), and decreased the expression of proinflammatory mediators, including IL-6, TNF-α, IL-1β, CCL2, and CXCL1. Similarly, in the spinal cord, curcumin reduced astrocyte and microglia activation, MAPK phosphorylation, and inflammatory cytokine and chemokine levels. Moreover, curcumin diminished p-ERK expression in DRG neurons and reduced c-Fos expression in the spinal dorsal horn. Collectively, these findings demonstrate that curcumin alleviates uterine pain by suppressing glial activation, MAPK signaling, and inflammatory mediators' production, ultimately reduces markers of neuronal activation and plasticity in the DRG and spinal cord. This provides mechanistic support for curcumin's potential in managing uterine pain.