Medical Pharmacology Chapter 13:  Pain Management:  Opioids

• Endogenous Opioid Peptides

  • The rationale for endogenous opioid peptides came from the idea that opioid receptors are probably present in the body for the purpose of interacting with endogenous or naturally occurring substances.  As a consequence, research proceeded to attempt identification of these naturally occurring substances now known as  ß-endorphins and related peptides.

  • Morphine (and related agents) cause analgesia by acting at the brain regions containing peptides which have opioid-like properties

  • Endogenous substances = endogenous opioid peptides

  • Previous used term "endorphin" now refers to ß-endorphins and related peptides derived from the precursor: prepro-opiomelanocortin

  • Most widely distributed opioid analgesic peptides:

    • Pentapeptides

      1. Methionine-enkephalin (met-enkephalin)

       

      1. Met-Enkephalin (2D top frame; 3D bottom frame)

      2. Leucine-enkephalin (leu-enkephalin)

  • Three major precursor proteins:

    • Prepro-opiomelanocortin (POMC) containing:

      • Met-enkephalin sequence

      • β-endorphin sequence

      • Some nonopioid peptides:

        1. ACTH

        2. β-lipotropin

        3. Melanocyte-stimulating hormone

    • Preproenkephalin (proenkephalin A ) containing:

      • Six copies of met-enkephalin

      • One copy of leu-enkephalin

    • Preprodynorphin (proenkephalin B) containing active peptides containing the leu-enkephalin sequence.

      • Dynorphin A

      • Dynorphin B

      • α and β neoendorphin

  • Endogenous opioid precursors which are localized at pain modulation brain regions are probably released during stress, including pain or pain anticipation.  

    • Also, precursor molecules for endogenous opioids are localized in adrenal medulla and gut neural plexuses.

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