Experimental Investigation of Fentanyl Analgesic Potency and Its Relationship with Endogenous Adrenaline Levels in Rats

Purpose: Fentanyl is a synthetic opioid analgesic widely used in perioperative medicine due to its high analgesic potency and short duration of action. Previous studies suggest that the analgesic and anesthetic effects of fentanyl may be associated with endogenous catecholamine levels. This study aimed to evaluate the relationship between fentanyl’s analgesic potency and anesthesia duration and endogenous levels of adrenaline (ADR) and noradrenaline (NDR) in rats, as well as changes in oxidative stress and inflammation markers including malondialdehyde (MDA), total glutathione (tGSH), and interleukin-6 (IL-6). Patients and Methods: Three groups of six rats each were formed: an intact group receiving fentanyl, an intact group treated with metyrosine, and an adrenalectomized group receiving fentanyl. Fentanyl was administered at doses of 2, 15, 30, and 75 µg/kg, and anesthesia duration was recorded following intraperitoneal injection. Analgesic activity was assessed by measuring pain threshold using the paw pressure method, and immobility in the supine position was evaluated as an observational parameter. ADR, NDR, MDA, tGSH, and IL-6 levels were biochemically measured in blood and tissue samples. Results: Fentanyl produced analgesic effects in all experimental groups. However, no distinct anesthetic effect sufficient for surgical procedures was observed. Although the durations of immobility in the supine position were recorded, these observations were not evaluated as a direct measure of anesthetic duration. Different doses of fentanyl did not lead to significant alterations in oxidative stress parameters, antioxidant capacity, or anti-inflammatory cytokine levels across the groups. Conclusion: In conclusion, although the analgesic effect of fentanyl increased in a dose-dependent manner, it was found to be independent of serum ADR and NDR levels. High-dose fentanyl (75 µg/kg) did not induce anesthesia and did not significantly affect oxidative stress markers (MDA, tGSH) or IL-6 levels. The increase in MDA and the decrease in tGSH observed in the absence of adrenal hormones support their indirect antioxidant role. Overall, the findings indicate that fentanyl modulates catecholamine responses depending on dose and hormonal status, while its analgesic effect appears to be primarily mediated through µ-opioid receptor activation. © 2026 Ates et al.