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Analgesia and Pain Management01:25

Analgesia and Pain Management

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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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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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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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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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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...
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Updated: Jun 14, 2025

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
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Morphine-responsive neurons that regulate mechanical antinociception.

Michael P Fatt1, Ming-Dong Zhang1, Jussi Kupari1

  • 1Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 65 Stockholm, Sweden.

Science (New York, N.Y.)
|August 29, 2024
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Summary
This summary is machine-generated.

Researchers identified a specific brain circuit in mice that controls pain perception. This circuit, involving brain-derived neurotrophic factor (BDNF), explains how opioids like morphine reduce mechanical pain.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Opioids are effective analgesics but their precise mechanisms for pain relief are not fully understood.
  • Opioid abuse has reached epidemic levels, necessitating a deeper understanding of their action.
  • The neuroanatomical basis for opioid-mediated analgesia requires further elucidation.

Purpose of the Study:

  • To identify the specific neural circuits in the brain responsible for opioid-induced pain relief.
  • To investigate the role of rostral ventromedial medulla (RVM) neurons in mechanical nociception.
  • To elucidate the molecular mechanisms underlying opioid analgesia.

Main Methods:

  • Single-cell transcriptomics was employed to analyze gene expression in neurons.
  • Manipulation of specific neuronal populations in the RVM was performed.
  • Morphine-induced antinociception was assessed in a mouse model.

Main Results:

  • An ensemble of neurons in the RVM was identified as critical for regulating mechanical nociception.
  • Activation or silencing of RVMBDNF projection neurons directly impacted morphine's pain-relieving effects.
  • A brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway and spinal galanin neurons were implicated.

Conclusions:

  • A specific RVM-spinal circuit regulates mechanical pain perception.
  • This circuit mediates the antinociceptive effects of morphine.
  • Understanding this circuit offers potential for developing targeted pain management strategies.