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Related Concept Videos

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 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...
Opioid Analgesics: Morphine and Other Natural Cogeners01:20

Opioid Analgesics: Morphine and Other Natural Cogeners

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...
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...
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...
Local Anesthetics: Clinical Application as Epidural Anesthesia01:29

Local Anesthetics: Clinical Application as Epidural Anesthesia

Epidural anesthetics are administered in the fat-filled epidural space, the outermost part of the spinal canal. This technique is commonly employed for pain management and anesthesia during lower abdomen and pelvis surgeries or labor and delivery.
Since epidural anesthetics can be infused through an epidural catheter, all types of drugs, including short-acting ones, can be administered. Chloroprocaine and lidocaine are examples of short and long-duration anesthetics, respectively. Bupivacaine...

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Peripherally acting opioids and clinical implications for pain control.

Nalini Sehgal1, Howard S Smith, Laxmaiah Manchikanti

  • 1University of Wisconsin School of Medicine and Public Health, Madison, WI 53595, USA. NSehgal@uwhealth.org

Pain Physician
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Summary

Peripheral opioid receptors in inflamed tissues offer pain relief without central nervous system side effects like addiction or respiratory depression. Research is exploring these receptors for novel pain treatments.

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Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Peripheral opioid receptors are present in the nervous system, non-neuronal tissues, and immune cells.
  • Inflammation increases peripheral opioid receptor synthesis and immune cell accumulation at injury sites.
  • Immune cells release opioid peptides that activate peripheral receptors, reducing nerve excitability and pro-inflammatory neuropeptide release.

Purpose of the Study:

  • To present the basis for peripheral opioid analgesia.
  • To describe current research on developing novel pain treatments targeting peripheral opioid receptors.
  • To highlight the potential for treatments with improved side effect profiles.

Main Methods:

  • Review of animal and human clinical studies on peripheral opioid receptor involvement in analgesia.
  • Analysis of mechanisms of opioid peptide release and activation of peripheral opioid receptors.
  • Examination of research on peripherally restricted opioid agonists.

Main Results:

  • Peripheral opioid receptor activation by local opioid agonists produces potent analgesia in inflamed tissues.
  • Analgesia occurs without central nervous system (CNS) involvement, avoiding CNS-mediated side effects.
  • Opioid receptors modulate inflammation, with potential anti-inflammatory effects, though mechanisms are not fully understood.

Conclusions:

  • Peripheral opioid analgesia offers a promising avenue for pain management by avoiding CNS side effects.
  • Development of peripherally restricted opioid agonists is a key research focus.
  • Further research is needed to fully understand the anti-inflammatory actions of opioids.