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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Analgesia and Pain Management01:25

Analgesia and Pain Management

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...
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

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, D-Pen5]-enkephalin or DPDPE for...
Signal Transduction: Overview01:26

Signal Transduction: Overview

Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...

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Related Experiment Video

Updated: Jun 26, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Rapid pain modulation with nuclear receptor ligands.

Jill C Fehrenbacher1, Jesse Loverme, William Clarke

  • 1Department of Endodontics, University of Texas Health Science Center, San Antonio, TX, USA.

Brain Research Reviews
|January 24, 2009
PubMed
Summary

Nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), rapidly control pain through non-genomic pathways. Ligands targeting PPARs and estrogen receptors offer new strategies for managing acute, chronic, inflammatory, and neuropathic pain.

Related Experiment Videos

Last Updated: Jun 26, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Nuclear receptors play a role in pain modulation.
  • Non-genomic signaling pathways are increasingly recognized for rapid cellular effects.
  • Peroxisome proliferator-activated receptors (PPARs), G-protein coupled receptor 30 (GPR30), and estrogen receptors are implicated in physiological processes.

Purpose of the Study:

  • To investigate the physiological and molecular mechanisms of nuclear receptor activation in pain control.
  • To emphasize the non-genomic effects of ligands on PPARs, GPR30, and classical estrogen receptors.
  • To explore the role of these receptors in acute, chronic, inflammatory, and neuropathic pain models.

Main Methods:

  • Administration of PPARalpha and PPARgamma agonists and antagonists in various pain assays.
  • Intrathecal administration of PPARgamma ligands in nerve injury models.
  • Assessment of GPR30 signaling in cultured sensory neurons.
  • Application of 17beta-estradiol conjugated to bovine serum albumin (17beta-E(2)-BSA) in trigeminal ganglion cultures.

Main Results:

  • PPARalpha agonists rapidly reduced acute and chronic pain, mediated partly by IK(ca) and BK(ca) channels.
  • Spinal PPARgamma activation by ligands rapidly attenuated hypersensitivity in neuropathic pain models.
  • GPR30 activation increased calcium accumulation in sensory neurons, potentially inducing hyperalgesia.
  • Non-genomic activation of estrogen receptors enhanced signaling pathways involved in pain.

Conclusions:

  • Nuclear receptor ligands, particularly PPARs, can rapidly modulate pain through non-genomic mechanisms.
  • Spinal PPARgamma activation plays a significant role in decreasing neuropathic pain.
  • Non-genomic actions of nuclear receptors represent a promising therapeutic avenue for pain management.