Evidence in mice that electroacupuncture reduces inflammation via specific neural pathways

"Most Western medicine has been focusing on blocking the neural pathways of pain to relieve the symptoms, but there are so many pain pathways and so many ways to open each of them," says senior author Qiufu Ma, a researcher at Harvard Medical School who has been studying the neuroanatomic basis of pain for years. Inspired by the core ideology of traditional Chinese medicine, which is to treat a disease by addressing the root cause, Ma and his team aim to target inflammation, a common source of human diseases and pain.

Previous studies have shown direct vagal nerve stimulations in the neck region can help reduce inflammation, but these experimental approaches require invasive procedures. With this in mind, Ma and his team set out to investigate whether and how electric stimulation using acupuncture, which only involves inserting thin needles through the skin, can modulate inflammation.

The team began by giving mice a 15-minute electroacupuncture at 3 mA at a specific site on the abdomen. This acupoint, dubbed ST25, has been associated with nerves of the spleen, which is a major organ involved in immune responses.

The team then simulated a life-threatening inflammatory condition that is often seen in patients suffering severe bacterial or virus infections by injecting mice with a compound called lipopolysaccharide (LPS). After injecting the treated mice with LPS, researchers found the serum levels of pro-inflammatory molecules in these animals was significantly lower than that of the control group. The mice's survival rates also more than doubled. However, when the team gave mice the electroacupuncture after the LPS shot, the treated mice had much greater inflammation than those that were untreated and did not survive.

By comparing the effect of electroacupuncture in mice with an altered nervous system, the team determined that high intensity stimulation at the abdomen could excite norepinephrine-producing nerves that connect the spine and spleen. The norepinephrine then activated a particular type of receptors in the spleen that suppressed pro-inflammatory molecules. But when LPS was introduced first, another type of splenic receptors -- pro-inflammatory in this case -- became highly expressed, and the subsequent electroacupuncture therapy further enhanced inflammation.

"We were really surprised to find that the same input has completely opposite outcomes in different disease stages," Ma says. "But a lot of the time, a patient would only come to us if they already have the disease. So we wanted to find out if there is a way to reduce inflammation as a treatment."

The team then conducted electroacupuncture at a different acupoint, this time on mice's hindlegs. They found stimulation at a low intensity of 0.5 mA for 15 minutes could significantly reduce pro-inflammatory molecule levels either before or after LPS-injection. Mice's survival rate after electroacupuncture also increased by 1-fold or more. A genetically modified mice model suggests that low-level electroacupuncture at hindlegs reduced inflammation not though the spleen, but a different neural pathway involving the vagus nerves and the adrenal glands.

"Our study illustrated that electroacupuncture has neuroanatomic basis, but its efficacy and safety on humans need to be validated in clinical trials," Ma says. "There's still many questions unanswered about this medical practice and thus a lot of room to do more research."

The work was supported by NIH grants, the Harvard/MIT Joint Research Program in Basic Neuroscience, and the Wellcome Trust grant.