Mechanistic insights into how Calcitonin gene-related peptide (CGRP) causes migraine and headache:  CGRP, a vasoactive peptide known to play a role in the pathophysiology of migraine, decreases the expression of PD-L1, aggravates acute and chronic pain, increases mechanical and thermal hypersensitivity and promotes nociceptive neuron excitability, via down-regulation of its target gene, 6/April/2019, 1.13 pm

An aspirin a day keeps cancer away, if so, what is the mechanism?: Probiotic-based chemotherapy targeting cancer stem cells and immune-inhibitory receptors in advanced metastatic cancers: A pharmaceutical mixture encompassing Aspirin, a nonsteroidal anti-inflammatory drug, and probiotic Lactobacillus rhamnosus increases the expression of tumor suppressor genes, such as CADM1/2, TIMP3, p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets ovarian cancer stem cells, confers protection against chemoresistance and prolongs survival, via up-regulation of its target gene, 6/April/2018, 1.00 pm
April 6, 2019
Which Antivirus Software is Best – Bitdefender or Avast?
April 8, 2019
Show all

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 Calcitonin gene-related peptide (CGRP) causes migraine and headache:  CGRP, a vasoactive peptide known to play a role in the pathophysiology of migraine, decreases the expression of PD-L1, aggravates acute and chronic pain, increases mechanical and thermal hypersensitivity and promotes 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:

The study presented here provides, for the firs time, mechanistic insights into how Calcitonin gene-related peptide (CGRP) causes migraine and headache. CGRP, by increasing the expression of its target genes, it may decrease PD-L1 levels (figs. 1-2). Thereby, it may: (a) aggravate acute and chronic pain; (b) increase thermal and mechanical hypersensitivity; (c) inhibit signal transduction cascade downstream of the PD-1 receptor; (c)  inhibit phosphorylation of SHP-1; (d) activate sodium channels; and (e) aggravate nociceptive neuron excitability.

Figure 1.Mechanistic insights into how Calcitonin gene-related peptide (CGRP)  causes acute and chronic pain. CGRP  decreases PD-L1 levels, increases thermal and mechanical hypersensitivity, inhibits phosphorylation of SHP-1,  activates sodium channels, and aggravates nociceptive neuron excitability.

Figure 2. Mechanistic insights into how Calcitonin gene-related peptide (CGRP) causes migraine and headache.

[/caption]

Together, this study suggests, for the first time, that Calcitonin gene-related peptide (CGRP) suppressors or inhibitors, either alone or in combination with other drugs, may be used to attenuate short-term 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/

Amount: $500#

Undisclosed mechanistic information: How CGRP increases the expression of PD-L1 and attenuates pain.

# Research cooperation


References:

Citation: Boominathan, L., Mechanistic insights into how Calcitonin gene-related peptide (CGRP) causes migraine and headache:  CGRP, a vasoactive peptide known to play a role in the pathophysiology of migraine, decreases the expression of PD-L1, aggravates acute and chronic pain, increases mechanical and thermal hypersensitivity and promotes nociceptive neuron excitability, via down-regulation of its target gene, 6/April/2019, 1.14 pm, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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

Courtesy: When you cite drop us a line at info@genomediscovery.org

Comments are closed.