Solving a thousand year-old mystery as to how Yoga therapy functions as a pain reliever: Mechanistic insights into how Yoga therapy functions as an adjuvant therapy for patients suffering from short- and long-term pain: Yoga therapy increases the expression of PD-L1, decreases Cox-2 and TRPV1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 21/June/2019, 6.29 pm

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Introduction:What they say:

A recent study from Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China; and Department of Neurobiology, Duke University Medical Center (DUMC), Durham, North Carolina, USA shows that “PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1.” This study was published in the 22 May 2017 issue of Nature Neuroscience (one of the best journals in Neurobiology with an impact factor of 16.724+) by Prof Ru-Rong Ji, Chen G and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Solving a thousand year-old mystery as to how Yoga therapy functions as a pain reliever: Mechanistic insights into how Yoga therapy functions as an adjuvant therapy for patients suffering from short- and long-term pain: Yoga therapy increases the expression of PD-L1, decreases Cox-2 and TRPV1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene


What is known?

It has recently been shown that blocking PD-1 with antibodies one could make tumors shrink. This work, relating to Cancer immunotherapy, has been chosen as Science’s breakthrough of the year. However, the work published recently, which is described below, may highlight the caveat in such an approach, as blocking PD-L1 may promote spontaneous pain and allodynia in cancer-bearing mice.

Prof. Ji has shown recently that: (1) Programmed cell death ligand-1 (PD-L1), produced by melanoma and normal neural tissues, inhibits acute and chronic pain; (2) injection of PD-L1 alleviates pain, and thereby functions as an analgesic agent; (3) Neutralization of PD-L1 or Block of PD1 promotes mechanical allodynia (hypersensitivity to pain); (4) PD1 null mice suffers from thermal and mechanical hypersensitivity; (5) PD-L1 promotes phosphorylation of SHP-1 and inhibits Sodium channels via PD-1 activation; and (6) PD-L1 inhibits nociceptive neuron excitability in dorsal root ganglion and thereby functions as a neuromodulator, suggesting that increasing the expression or the level of PD-L1/PD1 may alleviate pain and thermal and mechanical hypersensitivity.


From research findings to therapeutic opportunity:

Yoga is practiced in India for over 7000+ years, however, the mechanistic basis of its therapeutic effect, in attenuation of pain sensitivity and pain among others, remains largely obscure for centuries.

This study provides, for the first time, mechanistic insights into how yoga therapy, practiced all over the world, incidentally, today happens to be the International Yoga Day, attenuates pain sensitivity, pain, and trauma.

Yoga therapy, by increasing the expression of its target genes, it increases PD-L1 levels (fig. 1). Thereby, it: (a) decreases Cox-2 (Cyclooxygenase-2) levels; (b) inhibits  TrpV1 [transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor and the vanilloid receptor 1] levels; (c) decreases acute and chronic pain; (b) alleviates thermal and mechanical hypersensitivity; (c) activates signal transduction cascade downstream of PD-1 receptor; (d) phosphorylates SHP-1; and (e) inhibits sodium channels and nociceptive neuron excitability.

Figure 1.Mechanistic insights into how Yoga therapy inhibits pain. Yoga therapy enhances PD-L1 levels, decreases COX-2 and TRPV1 expression, suppresses thermal and mechanical hypersensitivity, phosphorylates SHP-1, inhibits activation of sodium channels, alleviates nociceptive neuron excitability, and attenuates pain.

Figure 2. While pharmacological activation of PD-L1 has been shown to attenuate acute and chronic pain, this study suggests that non-pharmacological/toxic intervention, such as yoga therapy, attenuates attenuates acute and chronic pain and trauma, through down regulation of Cox-2 and TRPV1, and up regulation of PD-L1.

Figure 3. Yoga therapy, popular in india and in other countries,  functions as an analgesic medication, through induction of PD-L1, and down regulation of Cox-2 and TRPV1.

Given the mechanistic basis of Yoga therapy (figs.1-3), in attenuating short- and long-term pain, physicians/orthopedicians/pain therapists may strongly consider encouraging their patients to undergo Yoga therapy.

Together, this study dispels, for the first time,  the molecular mechanism through which Yoga therapy functions as a pain medication; and why it should be promoted as an adjuvant therapy in patients suffering from short- and long-term pain (fig.3).


Details of the research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $1, 500#

Undisclosed mechanistic information: How yoga therapy increases the expression of PD-L1, decreases Cox-2 and TRPV1

# Research cooperation


References:

Citation: Boominathan, L.,   Solving a thousand year-old mystery as to how Yoga therapy functions as a pain reliever: Mechanistic insights into how Yoga therapy functions as an adjuvant therapy for patients suffering from short- and long-term pain: Yoga therapy increases the expression of PD-L1, decreases Cox-2 and TRPV1, attenuates acute and chronic pain, and suppresses mechanical and thermal hypersensitivity and inhibits nociceptive neuron excitability, via up-regulation of its target gene, 21/June/2019, 6.29 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

Web: http://genomediscovery.org or http://newbioideas.com

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