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Basic Research
Acupuncture Consensus

Acupuncture Analgesia Hypothesis

Opioid Inhibitory Control

It is evident that needling simulates peripheral nerves in the muscles which send messages to the brain to release endorphins (morphine-like peptides in the brain) These neurochemicals then cause analgesia by blocking the transmission of painful messages. Three main sites for endorphin acupuncture analgesia have been found. The pituitary gland is one site that has been shown to release endorphins into the blood stream. This hormone travels to the three parts of the brain and spinal cord to block the transmission of painful messages. The second site is the periaqaductal gray neurons in the mid brain which release endorphins that act as local transmitters to excite the rostral ventromedial medulla. The rostal ventromedial medulla in turn projects massively and selectively to pain transmitting neurons in the dorsal horn of the spinal cord and the trigeminal nucleus caudalis. Electrical stimulation in the periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) produces behavioral analgesia and inhibitions of spinal pain transmission. This third site, spinal cord endorphin system, is where the spinal cord neurons release endorphins to block the release of neurotransmitters from afferent fibers carrying painful messages to the cord.

In 1977, research showed that acupuncture analgesia inhibited the spinothalamic tract neurons from responding from painful inputs. This acupuncture effect was then blocked by naloxone, an endorphin receptor blocker. It has also been shown in mice and humans that naloxone blocked acupuncture anesthesia using behavior measurements. Acupuncture research has progressed since the 1970's to date to have no less than 17 different lines of evidence convergent upon acupuncture endorphin mechanisms verifying and supporting acupuncture analgesia.

17 Lines of Convergent Evidence of Acupuncture Endorphin Analgesia

  1. naloxone blocked acupuncture analgesia
  2. six opiates antagonist block acupuncture analgesia
  3. dextro-naloxone doesn't block acupuncture analgesia
  4. antibodies to endorphins block acupuncture analgesia
  5. micro-injection of naloxone blocks acupuncture analgesia
  6. genetic defects in opiate receptors causes less acupuncture analgesia
  7. deficiency in endorphins causes less acupuncture analgesia
  8. endorphins rise in cerebral spinal fluid and drop in the brain after acupuncture analgesia
  9. acupuncture analgesia is enhanced by protecting from enzyme destruction
  10. cross circulation of acupuncture analgesic effects
  11. reduce pituitary endorphins block acupuncture analgesia
  12. a rise in mRNA for proenkephalin with acupuncture analgesia
  13. C-fos gene protein rises in endorphin areas of brain
  14. acupuncture analgesia shows cross tolerance with morphine addiction
  15. acupuncture analgesia works best for emotional pain like endorphin
  16. lesions of arcuate nucleus blocks acupuncture analgesia
  17. lesions of periaquaductal gray blocks acupuncture analgesia

The considerable evidence for the three pathways shown above provides convincing proof that acupuncture analgesia is a known physiological phenomenon that can occur and be manipulated through the use of acupuncture needles and electrical stimulation.

Testing the involvement of the pituitary, several experiments were carried out, both surgically removing the pituitary and suppression of the pituitary endorphins by chemical manipulations, all of the experiments suppressed acupuncture analgesia in animals. Experiments to test the involvement of the mid brain was done since it has been shown that morphine pain relief was largely mediated by this system. Such experiments include direct lesions to the raphe by cutting the output fibers in the dorsal lateral tract, the spinal cord blockade of serotonin receptors, blockade of serotonin synthesis and direct micro-injection of naloxone into the mid brain; all of these experiments reduced acupuncture analgesia.

Enhancement of serotonin synthesis increased acupuncture analgesia. An experiment measuring serotonin showed an increase product (serotonin) was released during acupuncture analgesia along with noradreneline.

Gate Control Theory and Diffuse Noxious Inhibitory Control
In pain research, inhibitory actions are of great intrest, since inhibition can potentially be used to reduce nociceptive transmission and hence pain. For example, it was found that weak mechanical stimulation of the skin or electrical stimulation of large myelinated primary afferents in either a peripheral nerve (e.g., low intensity, high frequency transcutaneous electrical nerve stimulation) or in the dorsal column of the spinal cord can produce pain relief. These observations were the basis for the Gate Control Theory of pain inhibition that was proposed by Melzark and Wall. The original circuit diagram for the spinal cord gate may be inaccurate, but the consequences of activating large afferent fibers are real.

Another mechanism for inhibition of nociceptive transmission was described by a research group in Paris that include LeBars and Besson. These investigators refer to this inhibitory mechanism as "Diffuse Noxious Inhibitory Controls" or DNIC for short. This mechnism involves the activation of nociceptors essentially anywhere in the body. Noxious stimulation reduces pain (e.g., counter-irritation, high intensity, low frequency TENS, acupuncture). The nociceptors activate ascending projection neurons, and these in turn activate brain stem neurons that give rise to descending pathways that inhibit dorsal horn nociceptive neurons.

Basic Research Labs

  • Helene M. Langevin, MD, University of Vermont

    • - Biomechanical Effect of Acupuncture Needling
    This investigation will lead to quantification of needle grasp by measuring the peak force required to pull out acupuncture needles inserted at acupuncture points and control points in 80 normal human volunteers. Needling operations will be carried out by a computer-controlled device, eliminating potential investigator bias. All needling parameters will be consistent with clinical practice. The investigators will also study varying dwell times after insertion and different types of needle manipulation. They will correlate the force required to ithdraw the needle with the depth of its insertion into muscle and subcutaneous tissue, which will allow determination of which tissue is most responsible for needle grasp.

  • Ji-Sheng Han, MD, Beijing Medical University

    • - Neurobiology of Acupuncture Analgesia
    This study is examining the effects of electroacupuncture on gene and protein expression in a rat model by exploring the regulation of the endogenous opioid system in the nervous system.

  • John C. Longhurst, M.D., Ph.D. Professor and Chair Department of Medicine, UC Irvine

    • - Effect of Acupuncture on Cardiovascular Diseases Its Mechanism and Clinical Application
    It has been reported that EA is effective in treatment of hypertension, hypotension, angina and cardiac arrhythmias. Previous experiments have shown that the modulatory effect of EA on the cardiovascular sympathetic neurons is related to stimulation group III and IV afferent fibers in somatic nerves. These afferent inputs activate neurons in the arcuate nucleus in the hypothalamus, to produce and release endorphins and to activate the opioid receptors in the periaqueductal gray and rostral ventrolateral medulla, thus decreasing sympathetic activity. Recent studies have begun to explore the physiological basis of EA on myocardial ischemia. Low frequency EA on Neiguan acupoint or stimulation of the median nerves underlying the Neiguan acupoint reduces myocardial ischemia by reducing myocardial oxygen demand (Circulation 1998, 97:1186). This inhibitory effect can be blocked by naloxone applied intravenously or microinjected into rVLM. (Am. J Physiol 1999, H2127). The order of potency for reversal of the blood-pressure lowering effect of EA by specific opioid antagonists appears to be : mu > delta > kapa opioid receptors.
    Future studies of neuronal mechanism of EA both in animal experiments and in patients with myocardial ischemia, arrhythmias and hypertension are warranted. These studies will allow a better understanding and may provide the ability to modulate the sympathetic nervous discharge activity that frequently precipitates coronary ischemia, arrhythmias and hypertension.

  • Norman M. Kaplan, MD, University of Texas Southwestern Medical Center

    • - Acupuncture and Hypertension: Efficacy and Mechanisms
    Acupuncture has been advocated as safe and effective treatment of essential hypertension and other cardiovascular disorders (e.g., heart failure, myocardial ischemia) that have sympathetic neural components. Using a randomized, double-blind placebo-controlled design for their Phase II trial, the investigators will test two major hypotheses: (1) electroacupuncture produces a long-lasting reduction in sympathetic nerve activity, thereby providing a safe and effective complementary treatment of human hypertension; (2) a major mechanism mediating the blood pressure lowering effect of acupuncture is the activation of somatic afferents, which trigger a naloxone-sensitive reflex suppression of central sympathetic outflow.

  • Meiji University of Oriental Medicine

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