Last updated: Tue, Mar 4, 2025
Among the neurotransmitters that are important in central nervous system pain processing are serotonin, glutamate, gamma-aminobutyric acid (GABA), cholecystokinin (CCK) and opiates. Serotonin and GABA are important transmitters in the descending modulatory system. Serotonin is usually an excitatory transmitter, and GABA is usually an inhibitory transmitter.
Several opiates (compounds with actions similar to opium or morphine) are created and used in the body. Internally-generated compounds are referred to as endogenous. Three classes of endogenous opiates are known: beta-endorphins, enkephalins, and dynorphins. The endogenous opiates are heavily involved in the pain system. In particular, they are used to activate descending inhibition in the PAG and the RVM. If opioids (opium-like substances) are injected into either of these areas, analgesia (reduced pain perception) results. Naloxone is a substance that blocks the receptors of opioids. If naloxone is injected into these same areas, endogenous analgesia doesn't occur.
Studies of the use of opiates by the brain when it is subjected to sustained pain have shown that opioids are used in the ACC, PFC, IC, thalamus, amygdala and PAG. This indicates that opioids are used not only in descending pain inhibition but also in other facets of pain processing. The researchers found substantial interindividual differences
in the amount of opioids that are bound when the pain systems are activated.1 Opiates are widely used in the body outside the pain system, including particularly in the endocrine systems.
CCK has actions that oppose the actions of opiates and promote nociception. It is associated with anxiety in the brain. Anxiety, in turn, can increase sensitivity to pain.