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Previous studies have reported that the analgesic effect of acetaminophen involves the recruitment of endogenous opioid pathways that lead to analgesic spinal-supraspinal self-synergy (Raffa et al., 2000), and the analgesic effects induced by intrathecal injection or intracerebroventricular injection of acetaminophen were attenuated by mu -, delta -, and kappa -opioid receptor antagonists (Raffa et al., 2004)