We now know that injuries of all kinds cause not just local inflammation at the site of the injury, but even distant inflammation within the spinal cord and brain.

Outside the brain, inflammation is driven by immune cells, especially mast cells and macrophages. Within the central nervous system (the spinal cord and brain), inflammation arises mainly from microglia, and to a lesser extent, from astrocytes.

One of the biggest advances in the understanding of chronic pain came when it was realized that injuries outside the nervous system (of the skin, muscles, organs and other tissues) rapidly activate inflammatory immune cells within the spinal cord and brain — especially within the pain circuits of these higher centers.

When those immune cells become active, they not only release inflammatory chemicals like cytokines, chemokines, and prostaglandins, but also a number of excitatory chemicals, such as glutamate, aspartate, and quinolinic acid.

These two processes induce inflammation and excitotoxicity (together called immunoexcitotoxicity) within the brain and spinal pain pathways.

They also create high levels of free radicals, lipid peroxidation products, and other chemicals — such as substance P, neurotrophins, and neurotransmitters — that are associated with chronic pain.

The nervous system contains approximately 1 trillion immune cells called glia cells, which include microglia, astrocytes, and oligodendroglia. That’s 10 times the number of neurons (100 billion).

In some instances, such as chronic pain, these immune cells can remain activated for years, or even decades. As long as those special immune cells are triggering immunoexcitotoxicity, a person’s pain will persist.

In addition, the longer the pain pathways are stimulated, the easier it is for pain signals to pass through pain centers. That is, the pain center network develops a memory of the persistent pain.

We also know that stress and depression can lead to chronic pain syndromes, including:

• Migraines

• Fibromyalgia

• Chronic widespread pain

• Complex regional pain

• Neuropathic pain syndromes

Studies have shown that depression and stress can both activate the brain’s microglia, resulting in immunoexcitotoxicity in the same way we see with painful stimuli.

Over time, this can result in the development of chronic pain problems in people who are depressed.

In fact, studies have shown that 30 percent to 60 percent of patients who suffer from major depression will eventually develop chronic pain conditions.

In the past, medical experts considered things like migraines, fibromyalgia, major depressive disorder, complex regional pain syndromes, and neuropathic pain as separate conditions with separate causes.

We now know that they have many overlapping features, especially changes within the brain.