Therapeutic Effects of Spent Ground Coffee Oil on Nociception, Anxiety- and Depression-Like Behaviors, and Inflammatory Mechanisms in a CFA-Induced Intraplantar Inflammation Model in Mice.

Spent ground coffee oil (SGCO), rich in antioxidants and bioactive compounds, exhibits anti-inflammatory and analgesic properties and therefore warrants investigation in inflammatory pain models. This study aimed to investigate the topical effects of SGCO on hyperalgesia, emotional behavior, and inflammation-related mechanisms in a Complete Freund's Adjuvant (CFA)-induced inflammation model. SGCO was extracted from spent coffee grounds via non-thermal plasma (NTP) and incorporated into a transdermal vehicle at 10%, 20%, and 30% (w/w). Female Balb/c mice (2 months old, n = 8/group) received daily topical applications of SGCO for 14 days after CFA-induced inflammation. Mechanical and cold nociception and paw edema were assessed. The concentration with the strongest antihyperalgesic effect (20%) was used in further experiments assessing mechanical conflict avoidance, anxiety- and depression-like behaviors, cytokine and oxidative parameters (paw, spinal cord, hippocampus, and prefrontal cortex), and inflammatory pathways in paw tissue. SGCO at 10%, 20%, and 30% produced significant antihyperalgesic effects without affecting paw edema, with 20% providing a sustained effect for 11 days. SGCO 20% was associated with reduced anxiety-like behavior, improved hedonic-like behavior without altering locomotion, and reduced pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor), myeloperoxidase activity, phospho-Akt1/2/3, and NLRP3 in paw tissue. Additionally, it decreased protein carbonyl levels while increasing sulfhydryl group levels in the prefrontal cortex and hippocampus. These findings indicate that SGCO modulates inflammatory and oxidative pathways associated with CFA-induced inflammation and produces measurable effects on nociceptive and behavioral outcomes. Although the magnitude of the effects was generally modest, SGCO obtained via NTP technology may represent a low-cost and environmentally sustainable source of bioactive compounds for further preclinical investigation.