Acupuncture eases pain in the limbs because it releases a natural molecule called adenosine, neuroscientists in the United States reported on Sunday.
The mechanism was discovered through experiments in lab mice, which were given an injection of an inflammation-inducing chemical in their right paw.
The researchers inserted fine needles below the midline of the mice's knee, at a well-known acupuncture location called the Zusanli point.
They rotated the needle gently every five minutes for 30 minutes, mimicking a standard acupuncture treatment.
During and just after this operation, levels of adenosine in the tissues surrounding the needle surged 24-fold. The mouse's discomfort - measurable by the rodents' response time to touch and heat - was reduced by two-thirds, they found.
The same test was carried out on mice that had been genetically engineered to lack adenosine. The acupuncture failed to have any effect, and the mice reacted in discomfort, as before.
The team then experimented with an adenosine booster. They gave mice a leukaemia drug called deoxycoformycin, which makes it harder for tissues to remove adenosine.
As a result, levels of adenosine accumulated in the muscles, nearly tripling the duration of the acupuncture's effectiveness.
"Acupuncture has been a mainstay of medical treatment in certain parts of the world for 4,000 years, but because it has not been understood completely, many people have remained skeptical," said Maiken Nedergaard of the University of Rochester Medical Center in New York, who headed the research.
Previous work has focussed on acupuncture's effectiveness on the central nervous system - the trunk of nerves in the spinal cord and brain - rather than the peripheral nervous system.
In the central nervous system, acupuncture creates signals that cause the brain to produce powerful anti-pain chemicals called endorphins.
The paper is published by the journal Nature Neuroscience.