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Last updated: Tue, Mar 4, 2025
Researchers are finding many of the biochemical processes involved in chronicity of pain.
Levels of the neurotransmitter glutamate in the insular cortex (IC) were found to have decreased in fibromyalgia patients after treatment of their pain. There was a strong relationship between the decrease in pain and the decrease in glutamate. At the same time, sensitivity to pain from pressure was reduced.1
A number of studies have observed a lower-than-normal level of binding of exogenous (injected or ingested) opioids in patients with a variety of pain conditions (including rheumatoid arthritis, neuropathic pain, and fibromyalgia). "Binding" here means the joining of the neurotransmitter with a receptor protein on the surface of a neuron. This can be measured with PET technology. (See Neuroimaging and Pain Measurement.)
After pain is reduced, binding of exogenous opioids returns to normal levels. The low level of binding under the influence of pain could be either because of a low number of available opioid receptors or because of a high level of endogenous opioid release. Analysis of cerebrospinal fluid showed elevated opioid levels in the fluid. This probably means that endogenous pain inhibition systems had been heavily engaged in these patients.2
Studies of the neurotransmitter dopamine have shown that dopamine activity is suppressed in some chronic pain conditions. Dopamine is believed to be important in endogenous pain modulation. One study found that although normals release dopamine in response to extended muscle pain, fibromyalgia patients don't.3
The PAG-RVM pain modulation system has a very complex biochemistry.4 The functional RVM neurons (ON-cells, OFF-cells, NEUTRAL-cells) have been found to respond in different ways to different chronic pain animal models (inflammation, arthritis, and so on). The details are being worked on, but of interest behaviorally is that these biochemical changes tend to facilitate pain, and the changes have durations measured in hours after being triggered.