Although the exact site and mechanism of action of
acetaminophen is not clearly defined, the central nervous
system is the active compartment, and it likely involves
central COX inhibition and cannabinoidergic effects,
along with indirect analgesic serotoninergic effects.10
Pain research efforts over the past 5 decades have not yet
yielded many other new analgesics for use in the perioperative
setting. Explanations for this include: a lack of a
mechanism-based classification of pain syndromes that
makes it difficult to generate testable hypotheses, an
inadequate predictive validity of animal models that
translate into pain outcomes in humans, and the Food
and Drug Administration’s (FDA) requirement of safety
and efficacy against placebo, rather than superiority to an
active comparator, which contributes to development of
“me-too” drugs.