Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Analgesia and Pain Management01:25

Analgesia and Pain Management

3.1K
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...
3.1K
Pain01:20

Pain

2.0K
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...
2.0K
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

1.5K
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...
1.5K
Nociception01:44

Nociception

34.9K
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.
34.9K
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

6.9K
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,...
6.9K
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

1.6K
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...
1.6K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Structure- and Ligand-Based Virtual Screening for Identification of Novel TRPV4 Antagonists.

Molecules (Basel, Switzerland)·2025
Same author

Insights into Molecular Interactions and Biological Effect of Natural Stilbenoids at the TRPA1 Ion Channel.

ChemMedChem·2024
Same author

Targeting TRP Channels for Pain, Itch and Neurogenic Inflammation.

International journal of molecular sciences·2024
Same author

Inhibition of Canonical Transient Receptor Potential Channels 4/5 with Highly Selective and Potent Small-Molecule HC-070 Alleviates Mechanical Hypersensitivity in Rat Models of Visceral and Neuropathic Pain.

International journal of molecular sciences·2023
Same author

Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1.

International journal of molecular sciences·2022
Same author

Advances in TRP channel drug discovery: from target validation to clinical studies.

Nature reviews. Drug discovery·2021

Related Experiment Video

Updated: Apr 15, 2026

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
09:38

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Published on: April 14, 2016

13.4K

Mapping the Extended Pain Pathway: Human Genetic and Multi-Omic Strategies for Next-Generation Analgesics.

Ari-Pekka Koivisto1

  • 1Orion Pharma, Orion Corporation, FI-20101 Turku, Finland.

International Journal of Molecular Sciences
|April 14, 2026
PubMed
Summary

Developing effective pain therapeutics faces challenges. This review highlights the need for precise target selection, considering genetic support, site of action, and drug distribution for better pain relief.

Keywords:
LY3526318NaV1.7NaV1.8SuzatrigineTRPA1VX993human geneticshuman painpain therapeuticstarget validation

More Related Videos

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
08:16

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Published on: October 6, 2022

8.4K
Development of Recombinant Proteins to Treat Chronic Pain
10:37

Development of Recombinant Proteins to Treat Chronic Pain

Published on: April 11, 2018

10.1K

Related Experiment Videos

Last Updated: Apr 15, 2026

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery
09:38

Determining Pain Detection and Tolerance Thresholds Using an Integrated, Multi-Modal Pain Task Battery

Published on: April 14, 2016

13.4K
Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
08:16

Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies

Published on: October 6, 2022

8.4K
Development of Recombinant Proteins to Treat Chronic Pain
10:37

Development of Recombinant Proteins to Treat Chronic Pain

Published on: April 11, 2018

10.1K

Area of Science:

  • Pain research and drug discovery
  • Neuroscience and molecular pharmacology
  • Translational medicine

Background:

  • Despite advances like suzetrigine for acute pain, challenges persist in translating promising analgesic targets, such as NaV and TRP channels, into effective patient therapies.
  • Current chronic pain treatments often have limited efficacy and adverse effects due to CNS action; nociceptor-specific targets are attractive but complicated by channel redundancy and anatomical site requirements.
  • Pain drug discovery is shifting from serendipity to molecular precision, driven by human genetics and multi-omics.

Purpose of the Study:

  • To review the complexities of pain pathway processing and the challenges in translating molecular targets into successful analgesics.
  • To examine why promising drug targets and compounds for pain management often fail in clinical translation.
  • To propose a framework for more reliable target selection and validation in pain therapeutics development.

Main Methods:

  • Review of the pain pathway, from peripheral nociception to central processing, emphasizing inflammation and sensitization.
  • Analysis of human genetics, multi-omics data (including DRG transcriptomics), and large biobanks to identify genetically supported pain targets.
  • Integration of human in vitro electrophysiology, pharmacokinetic/pharmacodynamic (PK/PD) analyses, and consideration of drug distribution (e.g., BBB/PNS penetration).

Main Results:

  • Human genetics and multi-omics reveal a mismatch between traditional pain targets and genetically validated candidates.
  • NaV channel redundancy in dorsal root ganglia (DRG) and the need for sufficient target engagement (e.g., >90-95% for NaV1.8) are critical.
  • Drug distribution and species differences significantly impact efficacy, suggesting centrally accessible targets may be necessary for robust analgesia.

Conclusions:

  • A practical framework for target validation is proposed, integrating genetic support, cell-type/site-of-action mapping, human-relevant assays, and species-appropriate models.
  • Successful pain therapeutics require genetically and anatomically aligned targets, tested with appropriate exposures and validated through rigorous methods.
  • Advancing validated targets offers the most promising path toward developing genuinely effective and safer pain medications.