Opioids (narcotics) have been used for many years. It’s counter-intuitive to think that a drug like naltrexone which blocks the effect of opioids can help manage chronic pain. We do have some understanding that LDN (Low Dose Naltrexone) helps with autoimmune conditions. Current literature in pain medicine supports the view that chronic pain, especially chronic nerve pain conditions such as Complex Regional Pain Syndrome, Reflex Sympathetic Dystrophy, Diabetic Peripheral Neuropathy are autoimmune based. A study done on treating Fibromyalgia pain with LDN showed a 30% reduction in symptoms. Below is a short description of the mechanism behind chronic nerve pain.
The Central Nervous system (CNS) is made up of nerves and cells called glia. The glias make up about 80% of the CNS while the nerves make up about 20%. The function of the glia is to provide immune protection and host defense to the CNS. Under normal conditions the glia remain in an inactive state. They become activated readily in response to infection or injury. The most important change that happens during inflammation of the brain and spinal cord (Central Nervous System) is activation of glia cells.
When glia cells are activated they trigger the release of certain chemicals known as pro-inflammatory and neurotoxic factors. These factors include several cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin one beta (IL1-β), fatty acid metabolites and free radicals such as nitric oxide and superoxide. In painful conditions such as Complex regional pain) and neuropathic pain, damage to the peripheral nerves shifts the glia to an activated state within the spinal cord.
The family of glia cells are made up of microglia and astrocytes. Each of these family members have a specific role. The microglia guard and protect the immune system and the astrocytes help maintain cell fluid balance which is important for the action of chemicals in the cells called neurotransmitters (needed to control nerve function). Glia are activated by trauma, injury, infection, 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 prepare