Considering tapentadol as a first-line analgesic: 14 questions.

Tapentadol is the newest centrally acting analgesic to be approved by the US FDA and regulatory bodies in other countries. It has been called the first-in-class of a novel-acting analgesic mechanism of action that combines µ-opioid receptor agonist activity with neuronal norepinephrine-reuptake inhibition in a single molecule. This duality of action should combine inhibition of ascending (afferent) pain-transmitting signals with activation of descending (efferent) pain-attenuating systems (e.g., diffuse noxious inhibitory controls). However, not all novel mechanisms of action impart the characteristics needed for an analgesic to be considered for first-line therapy. These key questions may help inform clinical decision making.