PAPupuncture duration of action and mechanism. (A) Acupuncture and an adenosine receptor agonist (CPA) have A1R-dependent antinociceptive effects that last for 1–2 hr . In contrast, PAPupuncture has antinociceptive effects that last for nearly a week following a single injection or longer following sequential injections. (B) PAPupuncture mechanism. Following peripheral injection, PAP locally inhibits nociception via an A1R and PLC-dependent pathway. The long-lasting effects of PAP can be transiently blocked with CPX (A1R selective antagonist) or U73122 (blocks PLC-dependent signaling), revealing that PAP generates adenosine and activates A1R for days without desensitizing receptors.