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Printable Handouts
Navigable Slide Index
- Introduction
- Pain
- Detailed view of pain processes
- The nociceptor terminal
- Inhibitory receptors
- Activation of opioid receptors
- Opioid receptors in intestinal neurons
- Brainstem G-protein-coupled K+ channels
- Avoidance of opioid side effects
- Dose-dependent reduction of pain by morphine
- pH in different tissues
- μ opioid receptor - fentanyl scaffold
- Hypothesis for NFEPP
- Increased NFEPP binding to MOR at low pH
- cAMP inhibition at increasing pH
- FRET following MOR activation
- Fentanyl vs. NFEPP at different pH values
- Fentanyl vs. NFEPP - in vivo experiments
- Conditioned place preference test
- Lack of side effects with NFEPP
- Thank you
Topics Covered
- Anatomical & physiological principles underlying nociception & pain
- Examples of GPCR mediating excitatory & inhibitory effects on pain sensation
- Cross-talk between excitatory & inhibitory intracellular signalling pathways (GPCR in sensory neurons)
- Adverse side effects mediated by opioid receptors in the nervous system
- Selective activation of peripheral opioid receptors on sensory neurons in injured tissues
- Computational simulation of dynamic opioid receptor-ligand interactions (normal vs. injured)
- Novel opioid ligand (NFEPP): analgesia in models of inflammatory pain without adverse side effects
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Stein, C. (2019, March 28). GPCRs and pain [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 5, 2024, from https://doi.org/10.69645/ZNKF1655.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dr. Christoph Stein, Commercial/Financial matters disclosed are [Funding: Federal Ministry of Education and Research (BMBF; 0316177B/C1, 01EC1403E/F) European Commission (EU FP7-HEALTH-2013-INNOVATION-1; No. 602891-2) Patents: US Patent 9133120 B2; European Patent 2 801 046
Other Talks in the Series: G Protein-Coupled Receptors (GPCRs) Signaling in Health and Disease
Transcript
Please wait while the transcript is being prepared...
0:00
Hi. This is Christoph Stein from Berlin,
Germany and I was asked to talk about G-protein-coupled receptors and pain.
0:11
Pain is the processing of sensory information and integrated in the brain.
So when you look at this slide all the way on top,
this is where the person perceives pain as an integrated response of
many different stimuli that start
in the periphery and end up in the central nervous system.
So now look at peripheral ending of the sensory neuron,
all the way at the bottom of this slide,
there are many many different stimuli that can initiate this nociceptive process.
So at this stage,
we talk about nociception which is the beginning of the signal that ends up in the brain.
You can see cytokines,
you can see proteases, bradykinin, keratinocytes,
many different types of physical stimuli, mechanical,
heat, cold and chemical stimuli.
All of these excite nociceptive neurons at the peripheral ending.
Thereafter, there is an action potential that is transmitted
by the primary afferent neuron towards the spinal cord
where it is transmitted via synaptic processes and
then gets transferred upwards to the central nervous system.
1:38
In this slide, you see a more detailed view of all the different processes
and the receptors, the G-protein-coupled receptors that play a role in this.
First of all, you see on A,
you see the sensation.
That means that in this case,
all the different stimuli that I just mentioned but also all the different receptors.
Most of them are G-protein-coupled receptors on
the primary afferent neuron at the nerve ending.
You can see several different examples of G-protein coupled receptors.
For example, the 5-HT, the serotonin receptor,
the B2R, the so-called the bradykinin receptor,
the H1R, the histamine receptor and another important inhibitory receptor,
the opioid receptor, all the way to the right.
On the lower part of this slide you see all the different stimuli
that are actually initiated by the primary afferent neuron.
Because the primary afferent neuron also by itself,
releases stimulatory substances for example,
substance P on the right side or CGRP,
calcitonin gene-related peptide on the left side.
They also activate different G-protein- coupled receptors
on different structures such as blood vessels or
mast cells or keratinocytes which then again
release stimulatory substances that can initiate nociception.
When you look at C on the right side,
we see the process that is happening in the spinal cord after
the action potential reaches the central ending of this primary afferent neuron.
There, you can see that again,
different transmitters are released.
For example, glutamate, substance P again,
CGRP again which themselves then activate G-protein-coupled receptors
on the so-called secondary neuron in
the spinal cord and transmit this nociceptive signal.