renaming this post, very interesting material

Discussion in 'Fibromyalgia Main Forum' started by SharonR, Sep 24, 2002.

  1. SharonR

    SharonR New Member

    Damaged tissue and nerves is thought to be caused by The Wind-Up Phenomenon. "Wind-up was described more than 30 years ago as progressively increasing activity in dorsal horn cells following repetitive activation of primary afferent C-fibres. In humans, temporal summation of repeated painful stimuli has been regarded as a psychophysical correlate of wind-up."

    In simpler terms, Windup refers to a neurological pathophysiological mechanism whereby pain "begets pain".

    This from the Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;

    <<<<
    Severe tissue or nerve injury can result in a chronic and inappropriate sensation of pain, mediated in part by the sensitization of spinal dorsal horn neurons to input from primary afferent fibers. Synaptic transmission at primary afferent synapses is mainly glutamatergic. Although a functioning excitatory synapse contains both alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsynaptic membrane, recent evidence suggests that dorsal horn neurons contain some "silent" synapses, which exhibit purely NMDA receptor-mediated evoked postsynaptic currents and do not conduct signals at resting membrane potential. Serotonin, which is released onto dorsal horn neurons by descending fibers from the rostroventral medulla, potentiates sensory transmission by activating silent synapses on those neurons, i.e., by recruiting functional AMPA receptors to the postsynaptic membrane. This phenomenon may contribute to the hyperexcitability of dorsal horn neurons seen in chronic pain conditions.
    >>>>

    So when the doctor says it's all in you mind, he's telling the truth. Pain comes from the mind. Long after the tissue has healed, the wind-up continues to cause pain. The NMDA receptors seem to be the main activator of chronic pain. Therefore inhibiting these receptors should stop chronic pain caused by wind-up. I did a medline search and found several articles detailing the use of ketamine. Ketamine is an old anesthetic drug, used by veterinarians for decades. This article shows its resurgence in human medicine. The point of the article is that doses much lower than anesthetic dosage were helpful in this patient.

    <<<<
    [Analgesic effect of ketamine in a patient with neuropathic pain]

    [Article in Norwegian]

    Oye I, Rabben T, Fagerlund TH.

    Farmakologisk Institutt, Blindern, Oslo.

    We report the effect of a single daily dose of ketamine in a 54 year old woman with fibromyalgia and severe post-traumatic neuropathic pain. A number of different approaches for pain relief had been tried with little effect. An intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam lead to analgesia which lasted for almost two days. Long-term analgesia was also obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules every night at bedtime. The patient has now used this dose for nine months. Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of ketamine causes a long-term depression of pain intensity in some, but not in all, patients suffering chronic pain. This effect is distinctly different from the short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain. The long-term depression of the intensity of chronic pain states may be due to a reversal of NMDA receptor-dependent long-term potentiation of synapses in central pain pathways. By giving ketamine as a single dose at night the mental side-effects are reduced or avoided.
    PMID: 8999575 [PubMed - indexed for MEDLINE]
    >>>>

    Because ketamine is known to inhibit NDMA receptors, drug companies are looking for medications that target these receptors. This also from Medline:

    <<<<
    Can patients with chronic neuropathic pain be cured by acute administration of the NMDA receptor antagonist amantadine?

    Eisenberg E, Pud D.

    Pain Relief Unit, Rambam Medical Center, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa.

    The treatment of neuropathic pain remains a challenge as it rarely leads to long-term relief of symptoms. We report three patients with chronic neuropathic pain, in whom acute administration of the N-methyl-D-aspartate (NMDA) receptor antagonist amantadine resulted in complete resolution of symptoms, presumably due to termination the central 'wind-up' phenomenon.

    PMID: 9520249 [PubMed - indexed for MEDLINE]
    >>>>


    So there's hope on the horizon.


    [This Message was Edited on 09/26/2002]
  2. SharonR

    SharonR New Member

    Damaged tissue and nerves is thought to be caused by The Wind-Up Phenomenon. "Wind-up was described more than 30 years ago as progressively increasing activity in dorsal horn cells following repetitive activation of primary afferent C-fibres. In humans, temporal summation of repeated painful stimuli has been regarded as a psychophysical correlate of wind-up."

    In simpler terms, Windup refers to a neurological pathophysiological mechanism whereby pain "begets pain".

    This from the Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;

    <<<<
    Severe tissue or nerve injury can result in a chronic and inappropriate sensation of pain, mediated in part by the sensitization of spinal dorsal horn neurons to input from primary afferent fibers. Synaptic transmission at primary afferent synapses is mainly glutamatergic. Although a functioning excitatory synapse contains both alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the postsynaptic membrane, recent evidence suggests that dorsal horn neurons contain some "silent" synapses, which exhibit purely NMDA receptor-mediated evoked postsynaptic currents and do not conduct signals at resting membrane potential. Serotonin, which is released onto dorsal horn neurons by descending fibers from the rostroventral medulla, potentiates sensory transmission by activating silent synapses on those neurons, i.e., by recruiting functional AMPA receptors to the postsynaptic membrane. This phenomenon may contribute to the hyperexcitability of dorsal horn neurons seen in chronic pain conditions.
    >>>>

    So when the doctor says it's all in you mind, he's telling the truth. Pain comes from the mind. Long after the tissue has healed, the wind-up continues to cause pain. The NMDA receptors seem to be the main activator of chronic pain. Therefore inhibiting these receptors should stop chronic pain caused by wind-up. I did a medline search and found several articles detailing the use of ketamine. Ketamine is an old anesthetic drug, used by veterinarians for decades. This article shows its resurgence in human medicine. The point of the article is that doses much lower than anesthetic dosage were helpful in this patient.

    <<<<
    [Analgesic effect of ketamine in a patient with neuropathic pain]

    [Article in Norwegian]

    Oye I, Rabben T, Fagerlund TH.

    Farmakologisk Institutt, Blindern, Oslo.

    We report the effect of a single daily dose of ketamine in a 54 year old woman with fibromyalgia and severe post-traumatic neuropathic pain. A number of different approaches for pain relief had been tried with little effect. An intramuscular test dose of 0.4 mg/kg ketamine combined with 0.05 mg/kg midazolam lead to analgesia which lasted for almost two days. Long-term analgesia was also obtained by 250 mg/kg ketamine hydrochloride taken orally in the form of capsules every night at bedtime. The patient has now used this dose for nine months. Ketamine is an NMDA receptor antagonist. A single sub-anaesthetic dose of ketamine causes a long-term depression of pain intensity in some, but not in all, patients suffering chronic pain. This effect is distinctly different from the short-lasting (10-30 min) analgesic effect in cases of acute nociceptive pain. The long-term depression of the intensity of chronic pain states may be due to a reversal of NMDA receptor-dependent long-term potentiation of synapses in central pain pathways. By giving ketamine as a single dose at night the mental side-effects are reduced or avoided.
    PMID: 8999575 [PubMed - indexed for MEDLINE]
    >>>>

    Because ketamine is known to inhibit NDMA receptors, drug companies are looking for medications that target these receptors. This also from Medline:

    <<<<
    Can patients with chronic neuropathic pain be cured by acute administration of the NMDA receptor antagonist amantadine?

    Eisenberg E, Pud D.

    Pain Relief Unit, Rambam Medical Center, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa.

    The treatment of neuropathic pain remains a challenge as it rarely leads to long-term relief of symptoms. We report three patients with chronic neuropathic pain, in whom acute administration of the N-methyl-D-aspartate (NMDA) receptor antagonist amantadine resulted in complete resolution of symptoms, presumably due to termination the central 'wind-up' phenomenon.

    PMID: 9520249 [PubMed - indexed for MEDLINE]
    >>>>


    So there's hope on the horizon.


    [This Message was Edited on 09/26/2002]
  3. dojomo

    dojomo New Member

    I had to read this just to see what an eye board was (tee hee)... but seriously it looks like an interesting concept.....and a new way of relieving symptoms......But don't you have to wonder what is causing the increase in dorsal horn activity....They say tissues and nerve damage......so what is causing that? Maybe this will help lead to an answer......great detective work Sharon.........I think that a lot of our pain is neurosomatic.....that's why all the normal testing in painful areas......................DJ
  4. SharonR

    SharonR New Member

    my mistake for not being more specific. I heard about this on public radio 6 months ago, but couldn't remember where or why it was so important. They are doing studies at the U of Missouri, so I am going to check it out, since that's only a 6 hour drive and I have a friend there.
    My body has a lot to remember in pain. Ron Hubbards book,
    Scientology is based upon cell and tissue recordings, he calls the process of releasing all this, "clearing". Say's the mind is on continuious tape, conciously or un.
    Smiles
    Sharon
  5. SharonR

    SharonR New Member

    Take a close look at what they are saying. memory factor!