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Related Concept Videos

Nociception01:44

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Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
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Analgesia and Pain Management01:25

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Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
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Pain01:20

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Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
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GPCR Desensitization01:12

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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Opioid Receptors: Overview01:22

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Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
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Related Experiment Video

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GPR171 Activation Modulates Nociceptor Functions, Alleviating Pathologic Pain.

Pyung Sun Cho1,2, Han Kyu Lee3, Young In Choi3

  • 1Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.

Biomedicines
|April 3, 2021
PubMed
Summary

Researchers identified G protein-coupled receptor 171 (GPR171) as a novel target for pain relief. Activating GPR171 on somatosensory neurons reduces pain signals, offering a new strategy for analgesic development.

Keywords:
GPR171TRP channelanalgesianociceptorpain

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Modulating somatosensory neuron function is key for pain management, necessitating new molecular targets.
  • Many G-protein-coupled receptors (GPRs) are deorphanized, but their roles in somatosensory nociception require further study.
  • Understanding GPRs' locations, activation effects, and signal transduction pathways is crucial for analgesic strategies.

Purpose of the Study:

  • To investigate the role of G protein-coupled receptor 171 (GPR171) in somatosensory neuron function and pain modulation.
  • To identify novel ligands for GPR171 and evaluate their potential as analgesic agents.
  • To elucidate the signaling pathway through which GPR171 affects nociception.

Main Methods:

  • Expression analysis of GPR171 in nociceptor subpopulations.
  • Identification and characterization of natural peptide and synthetic chemical ligands for GPR171.
  • Assessment of GPR171 activation effects on nociceptive ion channel activity via Gi/o-coupled signaling.
  • Evaluation of GPR171 ligand efficacy in alleviating acute and pathological pain models.

Main Results:

  • GPR171 is expressed in a subpopulation of somatosensory neurons.
  • Activation of GPR171 by its ligands attenuates pain signals through Gi/o-coupled modulation of nociceptive ion channels.
  • Both natural and synthetic GPR171 ligands effectively alleviate acute and pathological pain at nanomolar to micromolar concentrations.

Conclusions:

  • GPR171 signaling in nociceptor neurons leads to pain alleviation.
  • GPR171 represents a promising molecular target for developing novel peripheral analgesics.
  • Targeting GPR171 offers a potential strategy for managing various pain conditions.