måndag 31 maj 2010

The secret behind acupuncture is adenosine?

Today an interesting report is reviewed in Science Daily. Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture by Nanna Goldman and collaborators.

In the central nervous system, acupuncture creates signals that cause the brain to churn out natural pain-killing endorphins. This effect has been known for along time. This research focuses on adenosine, a natural compound known for its role in regulating sleep, for its effects on the heart, and for its anti-inflammatory properties. But adenosine also acts as a natural painkiller, becoming active in the skin after an injury to inhibit nerve signals and ease pain in a way similar to lidocaine. It is also possible to triple the beneficial effects of acupuncture in mice by adding a medication approved to treat leukemia in people.

What are the messages of all these chemicals? Endorphins gives also a stress-reaction. What tells adenosine? The study is cited by 64 articles.

In the current study, scientists found that the chemical is also very active in deeper tissues affected by acupuncture.

The team made a number of observations regarding adenosine:

- In mice with normal functioning levels of adenosine, acupuncture reduced discomfort by two-thirds.
- In special "adenosine receptor knock-out mice" not equipped with the adenosine receptor, acupuncture had no effect.
- When adenosine was turned on in the tissues, discomfort was reduced even without acupuncture.
- During and immediately after an acupuncture treatment, the level of adenosine in the tissues near the needles was 24 times greater than before the treatment.

Once scientists recognized adenosine's role, the team explored the effects of a cancer drug called deoxycoformycin*, which makes it harder for the tissue to remove adenosine. The compound boosted the effects of acupuncture treatment dramatically, nearly tripling the accumulation of adenosine in the muscles and more than tripling the length of time the treatment was effective.

*inhibition of deaminase activity enhances increases in adenosine and prolongs anti-nociception actions of acupuncture. Two major pathways involved in extracellular enzymatic degradation of AMP. The nucleoside analog deoxycoformycin inhibits both AMP deaminase (AMPD) and adenosine deaminase (ADA).

Acupuncture triggers an increase in the extracellular concentration of ATP, ADP, AMP and adenosine. 
Acupuncture triggers an increase in the extracellular concentration of ATP, ADP, AMP and adenosine. From Nature.

"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, who led the research.

In fact acupuncture is a very fast developing discipline today, in spite of its old age.

This is just one way acupuncture could work.

A centrally acting agent cannot explain why acupuncture is conventionally applied in close proximity to the locus of pain and why the analgesic effects of acupuncture are restricted to the ipsilateral side.

Acupuncture triggers adenosine and ATP metabolites release
ATP is released in response to either mechanical and electrical stimulation or heat. Once released, ATP acts as a transmitter that binds to purinergic receptors, but ATP cannot be transported back into the cell but is rapidly degraded to adenosine. Thus, adenosine acts as an analgesic agent that suppresses pain through Gi-coupled A1-adenosine receptors.

Injury-signal: Damage is associated with an increase in extracellular nucleotides and adenosine. 'Similar to other types of tissue injury, accumulation of nucleotides in the interstitial space during acupuncture is probably a consequence of unspecific membrane damage or opening of stress-activated channels', says the study. This also Helene Langevin said, and it is true for many therapies, and also used by Nature herself.

Robert Becker in 'The Body Electric' showed a 'current of injury', a very small DC-current.

The relatively high extracellular concentration of ATP metabolites compared with ATP likely reflects the rapid enzymatic degradation of ATP. ATP is about 100-fold higher than AMP and adenosine in cytosol, and that only a fraction of AMP is dephosphorylated to adenosine. Although acupuncture has been practiced for over 4,000 years, it has been difficult to establish its biological basis. Our findings indicate that adenosine is central to the mechanistic actions of acupuncture. We found that insertion and manual rotation of acupuncture needles triggered a general increase in the extracellular concentration of purines, including the transmitter adenosine.

Deqi deactivates areas within the brain that are associated with the processing of pain. "The results are fascinating. Whether such brain deactivations constitute a mechanism which underlies or contributes to the therapeutic effect of acupuncture is an intriguing possibility which requires further research."
Because ATP is released during acupuncture the pinching sensation may be mediated by nociceptive P2X3 receptors, which are expressed by small-diameter, primary afferent neurons, some of which are sensitive to capsaicin, says the new study, concentrating on peripheral nerves.

Why is this a big piece of the puzzle?
Adenosine is shown to be important for the quantum biology in photosynthesis, where the enzyme ATPase has electrons quantum tunnelling. Also in biology the quantal aspect is very important, for the coherence and synergy, and hence for the regulation of biological molecular machines. The degrees of freedom responsible for the entropic Yin/Yang cycle is also dependent on the quantum biology.

Quantum tunnelling is important for our perceptions, which are electromagnetic and quantal.

The ratio of purines/pyrimidines also tells something about the functional states, not only in genes.

Receptors was shown to be crucial (GCPRs), and receptors need ATP, and are often using hexamer and pentamer rings. Water is hexameric. The hexamers change the magnetic moment very fast.

One may speculate that other non-allopathic treatments of chronic pain, such as chiropractic manipulations and massage, modalities that involve the mechanical manipulation of joints and muscles, might also be associated with an efflux of cytosolic ATP that is sufficient to elevate extracellular adenosine. As in acupuncture, adenosine may accumulate during these treatments and dampen pain, says the discussion.

The acupuncture and other therapies are often called 'Energy medicine', something that mainstream dislike strongly. Any hint at diffuse energy is non-scientific, according to them. Well, they are wrong.

Asghar et al. Acupuncture needling sensation: The neural correlates of deqi using fMRI. Brain Research, 2010; 1315111 DOI: 10.1016/j.brainres.2009.12.019
Science Daily in febr Study Maps Effects of Acupuncture On the Brain
and in may Acupuncture's Molecular Effects Pinned Down: New Insights Spur Effort to Boost Treatment's Impact Significantly.
Radiological Society of North America. Nina Theysohn "Acupuncture changes brain's perception and processing of pain, researchers find." /ScienceDaily, 30 Nov. 2010. Web. 25 Aug. 2011.
University of York York study maps the effects of acupuncture on the brain,
Nature article  Adenosine A1 receptors mediate local anti-nociceptive effects of acupuncture, Nanna Goldman et al., Nature Neuroscience 13, 883–888 (2010)

1 kommentar:

  1. New Scientist had a Short Sharp Science note too.

    "Far from improving energy flow of "chi", the study suggests that pain relief from the ancient Chinese technique, in which fine needles are inserted into the skin, is down to adenosine - a molecule which is known to have anti-inflammatory properties."

    But this adenosine is a part in ATP, the energy molecule, so "chi" can very well be seen as an "energy flow".

    ATP is also a "quantum biological" molecule. See http://tgd.wippiespace.com/public_html/bioware/bioware.html#wormc

    A google search with quantum biology ATP adenosine gives many hits.

    Davies in Quantum Fluctuations and Life, 2004, http://arxiv.org/ftp/quant-ph/papers/0403/0403017.pdf
    "there are fundamental aspects of quantum mechanics that go beyond this description, such as:
    a. Superpositions and various aspects of quantum phases, such as resonances.
    b. Entanglement.
    c. Tunneling.
    d. Aspects of environmental interactions, such as the watchdog and inverse watchdog effects.
    e. Abstract quantum properties such as supersymmetry."

    Biological molecules are assumed to store and process classical bits rather than qubits. The actin enzyme moves along the myosin filament in muscle cells (it also plays a role in neurons), powered by ATP. Quantum coherence is at work over a long enough range to encompass several adjacent molecules.

    This is a qubit, entangled over time, then decohered.

    See also Davies 2008: A quantum origin of life. http://www.worldscibooks.com/etextbook/p581/p581_chap01.pdfin Quantum aspects of Life, http://www.worldscibooks.com/physics/p581.html