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This video is adapted from: https://youtu.be/xkMP4eXp1Oc
The periaqueductal gray, or PAG, is an area of gray matter that surrounds the cerebral aqueduct in the brainstem. Although it is associated with a number of functions, it is best known for its role in analgesia, or pain reduction. In this video, I discuss the PAG and the pathway by which it is thought to be able to inhibit pain signals from the spinal cord.[1]
The PAG is an area of gray matter found in a part of the brainstem called the midbrain. The PAG surrounds a structure called the cerebral aqueduct, hence the name “periaqueductal.” There are a number of functions that have been connected with the PAG, including the regulation of heart rate and blood pressure, management of autonomic processes like bladder control and contraction, production of vocalizations, and production of fearful and defensive reactions. The PAG is best known, however, for its role in analgesia, or pain reduction.
Since the 1960s, the PAG has been known to play a role in analgesia, and stimulation of the PAG has been observed to inhibit pain in both rodents and humans. The mechanisms underlying this PAG-induced analgesia are not completely understood, but the main pathway is thought to involve neurons that project from the PAG to serotonin-producing neurons of the medulla oblongata known as the raphe nuclei. These activated raphe nuclei neurons project down to the dorsal horn of the spinal cord where they inhibit neurons that are responsible for transmitting pain signals. In this way, they inhibit the ability of pain signals to reach the brain.
Through this pathway, the PAG is thought to be able to inhibit pain naturally---a phenomenon that may occur, for example, in situations of extreme stress like that experienced by soldiers in battle. The pathway may also be involved in analgesia that occurs as part of the placebo effect, or in other scenarios where we experience a capacity to control pain through top-down mechanisms. Additionally, the PAG is rich in opioid receptors and believed to play an important role in the analgesia elicited by opioid drugs.