fection, opioids. When activated, glia release pro-inflammatory and neurotoxic factors (cytokines).
Drugs that block the effect of opioids (morphine) may help prevent activation of glia. Such drugs are naltrexone and naloxone. Low dose naltrexone (hence, LDN) may inhibit the activation of glia.
Cells use chemicals called neurotransmitters to communicate with each other. Like most drugs, neurotransmitters work by attaching to specific receptors on cells. When neurotransmitters attach to receptors on cells, it allows for the passage of other substances into the cell (such as sodium, calcium). When these substances enter the cells they trigger the cells to fire and transmit signals along the nerve fiber.
Glutamate is the most abundant neurotransmitter found in the central nervous system. It is an excitatory neurotransmitter. Glutamate binds to a receptor called NMDA (N-methyl D-aspartate).
The NMDA receptor is the most common receptor found in the Central Nervous System. When the NMDA receptor is activated by glutamate it opens up calcium channels which cause the nerves to fire.
To summarize, when glial cells are activated they release chemicals and neurotransmitters that cause NMDA receptors to be activated which cause nerves to fire.
LDN (Low Dose Naltrexone), by its ability to inhibit microglial activation, suppresses activation of NMDA receptors by decreasing the release of glutamate neurotransmitter.
Whether to try LDN for CRPS must be seriously considered, especially since it can have interactions with existing medical regimens, particularly if medications are opioids (morphine like drugs). It should not be taken by patients who are on opioids or tramadol. Often, the choice is easiest for patients who are not on opioids. Fortunately, LDN has a low risk of side effects before taking LDN, one must consider current research, clinical trials, strength of anecdotal reports, severity of CRPS, response to other therapies, drug interactions and any contraindications.
Most physicians are unfamiliar with LDN. Be prepared to discuss LDN with your physician and acquaint him or her. There are some resources at the end of this article to help you acquaint yourself and your physician.
LDN does not work immediately. It may take anywhere from a few weeks to many months. Users have reported to notice a difference after 9 to 12 months. After the initial response, it continues to show a benefit. The main goal of LDN is to slow or halt the progression of disease. In addition, symptoms may improve. Improvements seen in pain include decreases in exacerbation of pain, symptom improvement, improved functioning and better tolerance to pain.
LDN may increase endorphins (morphine like substances produced by the body) which may result in a feeling of well being. Human trials have demonstrated improvement in mood and in quality-of-life scores. This feeling helps lower stress, reduce depression, and increase healing. This is especially true for conditions like CRPS where stress can lead to exacerbations.
Naltrexone was initially tested in humans for safety at the 50 to 100 mg dose level. There have been a number of studies such as a Crohn's disease study. Studies have assessed naltrexone administered at low-dose for safety and found no major issues to date.
Physicians who prescribe LDN feel that at such a low dose, it is unlikely to cause any harm. At high doses (50mg to 300mg of naltrexone) it may affect the liver. Patients with pre-existing liver and kidney conditions using LDN should have their metabolic functions monitored by their doctors.
No studies have been done to see the long term effects of LDN and its intermittent opioid blocking effect. Naltrexone has different effects when used in high doses and it is unknown whether the long-term use of LDN could have effects similar to those of high dose naltrexone. Patients who are considering taking LDN long term should approach with caution if they do not have a serious condition.
LDN does not stay in the body very long, hence if an emergency arises and a patient has to be administered an opioid 