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Welcome to 2 minute neuroscience, where I explain neuroscience topics in 2 minutes or
In this installment I will discuss the periaqueductal gray, or PAG.
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
Additionally, the PAG is rich in opioid receptors and believed to play an important role in
the analgesia elicited by opioid drugs.