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, Durham, North Carolina, US 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 Ji RR, 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: Mechanistic insights into how chronic stress aggravates pain sensation and pain: Chronic stress decreases the expression of PD-L1, aggravates acute and chronic pain, and increases mechanical and thermal hypersensitivity and aggravates nociceptive neuron excitability, via down-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:
Although it is known for years that chronic stress aggravates pain sensation and pain, the mechanistic basis of which remains largely obscure. The study presented here provides, for the first time, mechanistic insights into how chronic stress aggravates pain sensation and pain.
Chronic stress, by increasing the expression of its target genes, it may decrease PD-L1 levels (fig. 1). Thereby, it may: (a) aggravate acute and chronic pain; (b) increase thermal and mechanical hypersensitivity; (c) inhibit signal transduction cascade downstream of PD-1 receptor; (c) dephosphorylate SHP-1; (d) activate sodium channels; and (e) increase nociceptive neuron excitability.
Given the mechanistic basis of how chronic stress (fig.1) may aggravate short- and long-term pain, physicians/orthopedicians may consider encouraging their patients, under severe stress, for a prolonged period, to undergo mindfulness meditation-based therapy, which may in attenuating acute and chronic pain (https://genomediscovery.org/2019/05/mindfulness-medication-based-pd-1-pathway-activation-for-pain-therapy-mindfulness-medication-increases-the-expression-of-pd-l1-attenuates-acutes-and-chronic-pain-and-suppresses-mechanical-and/).
Together, this study provides, for the first time, mechanistic insights into how chronic stress may aggravate pain sensation and pain (Figure 2-3); and how mindfulness meditation may function as an adjuvant therapy for patients suffering from short- and long-term pain.
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/
Undisclosed mechanistic information: How chronic stress decreases the expression of PD-L1 and aggravates pain
# Research cooperation
Citation: Boominathan, L., Mechanistic insights into how chronic stress aggravates pain sensation and pain: Chronic stress decreases the expression of PD-L1, aggravates acute and chronic pain, and increases mechanical and thermal hypersensitivity and aggravates nociceptive neuron excitability, via down-regulation of its target gene, 28/May/2019, 10. 52 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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