University of Minnesota researchers provide hope for patients with sickle cell disease (SCD) with a milestone in acupuncture pain control research. Electroacupuncture induced pain relief for SCD was confirmed in a controlled laboratory experiment. In addition, biochemical changes (amyloid P, IL-1beta, substance P, tryptase, mast cell activation, p38MARK) reveal important electroacupuncture analgesic pathways. Lead researcher Dr. Wang from Dr. Gupta's lab is encouraged by the success of the study and notes, "We will be continuously working on the scientific mechanisms of acupuncture treatment in reducing the dose usage of opioids in multiple pain conditions."

A milestone in acupuncture laboratory research, the first-ever method to perform electroacupuncture on conscious, freely moving, unrestrained mice has been developed. Using this groundbreaking technique, Dr. Ying Wang, M.D., Ph.D., L.Ac. and her co-workers from the University of Minnesota (Department of Medicine) demonstrate a significant analgesic effect caused by the application of electroacupuncture in transgenic mouse models of sickle cell disease (SCD) with electroacupuncture treatment.

Dr. Wang notes, "The meaning of our research is: humans can control their motion and thus can stay still without the use of any restraint/anesthetics. Conversely, rodents do not voluntarily decrease their movement when they are treated with acupuncture and thus acupuncture has traditionally been performed in restrained or anesthetized mice or rats. However, the influences from using restraint or anesthetics on the effect of acupuncture are hard to ?predict. In our new model, the animal is freely moving (which mimics its natural environment) and we believe this free-moving natural state more closely mimics a human patient’s status of ‘freedom’ during treatment. We have also successfully applied electroacupuncture in conscious, free-moving mice with transgenic cancer pain or chemical irritant-induced inflammatory pain syndromes, and we will apply to more rodent pain models, especially transgenic mice pain models."

Sickle cell disease (SCD) is a chronic condition that causes blockage of blood vessels and deprives healthy tissue of oxygen, which causes severe acute pain attacks, called pain crises.  Over 60,000 babies are born every year with SCD in the U.S. SCD can affect every racial/ethnic population, but incidence of the disease in the U.S. is highest among African Americans with 73.1 cases per 1,000 births.

There is no universal cure for SCD and treatment options are limited. Severe pain crises are often treated with prescription opioids like oxycodone, OxyContin, methadone and morphine. The acute and chronic pain associated with SCD is often undertreated or inappropriately managed. Sickle pain can be excruciating.

Many sickle patients live with heightened chronic pain, and most suffer from unanticipated attacks of severe, acute pain, called pain crises. Sickle pain has traditionally been treated with opioids, which can have unintended negative consequences including building a tolerance and potential for addiction and/or abuse. Safer, natural, non-addictive pain management treatments are important for SCD patients and medical providers, including licensed acupuncturists. Scientific research for acupuncture in sickle pain relief is rare. This investigation moves scientific understanding forward for the treatment of SCD; we can now measure biochemical mechanisms active in pain relief provided by electroacupuncture.

In the acupuncture investigation for sickle pain relief entitled Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms, it was documented that electroacupuncture significantly ameliorates several key inflammatory and nociceptive mediators. This includes amyloid P, IL-1beta, substance P, tryptase, mast cell activation, and p38MARK both peripherally and centrally in sickle mice correlative to the antinociceptive response. Dr. Wang and her colleagues have established the concept of "individual differences" between mice that have variable responses to electroacupuncture. The treated mice can be categorized into high responders, moderate responders, and non-responders according to their pain relief compared with the baseline prior to acupuncture treatment.

The researchers observed a gender difference for pain relief; female mice exhibited a fluctuating anti-hyperalgesic effect during some treatments while male mice displayed relatively stable pain relief responses. Although the scientific mechanisms of gender variation are not completely understood yet, these findings implicate individual differences associated with acupuncture treatment; i.e., the optimized effect on the human body from acupuncture requires an individual treatment plan (e.g., acupoint selection, acupuncture needle manipulation, treatment duration, etc.).

Clinical trials demonstrate that opioid requirements are reduced post-surgically as a result of pre-operative acupuncture treatments. This is supportive of Dr. Wang’s results in the publication, that application of sub-optimal doses of morphine in electroacupuncture treated moderate responders produced equivalent antinociception as obtained in high responders without the need for addition of morphine. This is a critical implication to reduce the opioid requirement in sickle pain patients. "We will be continuously working on the scientific mechanisms of acupuncture treatment in reducing the dose usage of opioids in multiple pain conditions," said Dr. Wang.

Electroacupuncture in conscious freely moving mice without anesthesia or restraint simulates acupuncture treatments on human patients, which offers a highly effective approach to develop a mechanism based understanding of acupuncture analgesia devoid of the influence of anesthetics or restraints. This study opens a new door for investigating acupuncture treatments in the laboratory and fundamentally changes the direction of acupuncture research for future studies.

References:
1. Ying Wang, Jianxun Lei, Mihir Gupta, Fei Peng, Sarah Lam, Ritu Jha, Ellis Raduenz, Al Beitz, Kalpna Gupta. Electroacupuncture in conscious free-moving mice reduces pain by ameliorating peripheral and central nociceptive mechanisms. Scientific Reports 6, 34493; doi: 10.1038/srep34493 (2016).

2. Ballas, S. K., Gupta, K. & Adams-Graves, P. Sickle cell pain: a critical reappraisal. Blood 120, 3647-3656, (2012).

3. Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK and et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517.

4. Kotani N1, Hashimoto H, Sato Y, Sessler DI, Yoshioka H, Kitayama M, and et al. Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting, analgesic requirement, and sympathoadrenal responses. Anesthesiology. 2001 Aug;95(2):349-56.