Preventive Effects of Avocado/Soybean Unsaponifiables on Complex Regional Pain Syndrome Type I in a Rat Model

<b>Background and Object:</b> Complex Regional Pain Syndrome Type I (CRPS-I) is a debilitating condition often triggered by trauma, with early pathophysiology driven by neuroinflammation and oxidative stress. Avocado/soybean unsaponifiables (ASU) possess potent anti-inflammatory and antioxidant properties but have never been tested for CRPS-I prevention. This study investigated the preventive effects of early systemic administration of ASU on the development of CRPS-I-like features in a validated rat model of tibial fracture and cast immobilization. <b>Methods:</b> Twenty adult male Wistar rats were randomized into two groups (<i>n</i> = 10/group): a CRPS-I (Vehicle) group receiving daily intraperitoneal saline, and a CRPS-I+ASU group receiving daily ASU (300 mg/kg/day). The model was induced via a right tibial fracture followed by 28 days of cast immobilization. Treatment began immediately post-fracture. Behavioral outcomes (mechanical allodynia via von Frey, paw edema, temperature asymmetry) were assessed pre-fracture and on day 29. Subsequently, levels of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and oxidative stress markers (TAS, TOS, OSI) were measured in the ipsilateral hind paw tissue. <b>Results:</b> ASU treatment significantly attenuated the development of CRPS-I-like manifestations. Compared to the vehicle group, the ASU group exhibited a markedly lower median percentage decrease in mechanical withdrawal threshold (30.20% [22.56-37.01] vs. 51.45% [47.84-61.11], <i>p</i> = 0.001), reduced temperature asymmetry (0.75 °C [0.55-1.00] vs. 1.95 °C [1.80-2.33], <i>p</i> < 0.001), and less paw edema (8.35% [7.06-11.29] vs. 14.75% [12.66-19.20], <i>p</i> = 0.004). Biochemically, ASU treatment significantly suppressed tissue levels of IL-1β, IL-6, and TNF-α (all <i>p</i> < 0.001), enhanced total antioxidant status (TAS), and reduced total oxidant status (TOS) and the oxidative stress index (OSI) (all <i>p</i> < 0.001). <b>Conclusions:</b> Early systemic administration of ASU significantly prevents the development of nociceptive, vascular, inflammatory, and oxidative disturbances in a rat model of CRPS-I. These findings highlight ASU's multimodal protective effects at the tissue level and position it as a promising candidate for early preventive intervention in post-traumatic CRPS-I.