Acetaminophen, aspirin, and caffeine combination works synergistically to provide pain relief and reduce inflammation in cluster headaches. Acetaminophen acts centrally to inhibit pain perception, aspirin suppresses prostaglandin synthesis and reduces inflammation, while caffeine enhances analgesic effects and promotes drug absorption by vasoconstriction and increased central nervous system stimulation. This combination targets multiple pain pathways to provide more comprehensive headache relief compared to individual components.