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Nociception01:44

Nociception

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. Thus, pain helps the...
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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...
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...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

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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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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...
Pain01:20

Pain

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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Selective opiate modulation of nociceptive processing in the human brain.

K L Casey1, P Svensson, T J Morrow

  • 1Department of Neurology, University of Michigan, Ann Arbor, Michigan 48109, USA.

Journal of Neurophysiology
|July 19, 2000
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Fentanyl (a mu-opioid receptor agonist) selectively reduces pain perception by suppressing brain responses to noxious cold, while leaving vibrotactile sensation unaffected. This indicates a targeted mechanism for opioid analgesia.

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Published on: July 29, 2014

Area of Science:

  • Neuroscience
  • Pharmacology
  • Pain Research

Background:

  • Fentanyl, a potent mu-opioid receptor agonist, is known to produce analgesia.
  • A key characteristic of fentanyl analgesia is its selective effect, leaving certain sensory modalities like vibrotactile sensation intact.
  • Understanding the neural mechanisms underlying this selective effect is crucial for optimizing pain management strategies.

Purpose of the Study:

  • To investigate the brain mechanisms responsible for fentanyl's selective analgesia using positron emission tomography (PET).
  • To compare the effects of fentanyl on brain responses to painful (cold pressor test) and non-painful (vibratory) stimuli.
  • To elucidate the role of specific brain regions, including the anterior cingulate cortex, in mediating opioid-induced analgesia.

Main Methods:

  • Healthy male subjects (ages 18-28) underwent PET scans to measure regional cerebral blood flow (rCBF).
  • Stimuli included painful ice water immersion and painless vibratory stimulation, administered before and after intravenous fentanyl or placebo injection.
  • fMRI data analysis focused on comparing rCBF changes associated with each stimulus type under different drug conditions.

Main Results:

  • Fentanyl significantly reduced pain intensity and unpleasantness, along with associated physiological responses.
  • Noxious cold stimulation activated several brain regions, including the thalamus, insular cortex, and S2 cortex, which were significantly attenuated by fentanyl.
  • Vibratory stimulation activated the primary sensory cortex (S1), and these responses were unaffected by fentanyl.
  • Fentanyl alone increased rCBF in the anterior cingulate cortex, particularly the perigenual region.

Conclusions:

  • Fentanyl selectively suppresses brain responses to noxious stimuli, consistent with a reduction in nociceptive spinothalamic transmission.
  • The anterior cingulate cortex, especially the mid-anterior region, plays a significant role in mediating fentanyl analgesia.
  • These findings support a targeted mechanism of opioid analgesia that spares non-painful sensory pathways.