US. Many acupuncturists attribute pain relief to the release of endorphins when needles penetrate, but no longer support the idea that acupuncture can affect a disease. Some studies suggest acupuncture causes a series of events within the central nervous system, and that it is possible to inhibit acupuncture's analgesic effects with the opioid antagonist naloxone. Mechanical deformation of the skin by acupuncture needles appears to result in the release of adenosine. The anti-nociceptive effect of acupuncture may be mediated by the adenosine A1 receptor. A 2014 review in Nature Reviews Cancer analyzed mouse studies that suggested acupuncture relieves pain via the local release of adenosine, which then triggered nearby A1 receptors. The review found that in those studies, because acupuncture "caused more tissue damage and inflammation relative to the size of the animal in mice than in humans, such studies unnecessarily muddled a finding that local inflammation can result in the local release of adenosine with analgesic effect." History Origins Acupuncture, along with moxibustion, is one of the oldest practices of traditional Chinese medicine. Most historians believe the practice began in China, though there are some conflicting narratives on when it originated. Academics David Ramey and Paul Buell said the exact date acupuncture was founded depends on the extent to which dating of ancient texts can be trusted and the interpretation of what constitutes acupuncture. Acupressure therapy was prevalent in India. Once Buddhism spread to China, the acupressure therapy was also integrated into common medical practice in China and it came to be known as acupuncture. The major points of Indian acupressure and Chinese acupuncture are similar to each other. According to an article in Rheumatology, the first documentation of an "organized system of diagnosis and treatment" for acupuncture was in Inner Classic of Huang Di (Huangdi Neijing) from about 100 BC. Gold and silver needles found in the tomb of Liu Sheng from around 100 BC are believed to be the earliest archaeological evidence of acupuncture, though it is unclear if that was their purpose. According to Plinio Prioreschi, the earliest known historical record of acupuncture is the Shiji ("Records of the Grand Historian"), written by a historian around 100 BC. It is believed that this text was documenting what was established practice at that time. Alternate theories The 5,000-year-old mummified body of Ötzi the Iceman was found with 15 groups of tattoos, many of which were located at