The periaqueductal gray (PAG) is a small, column-shaped region of gray matter situated deep within the brainstem. This structure integrates information from higher brain areas, such as the cortex and amygdala, and translates those signals into automatic physical responses. It acts as a central hub for regulating internal body states and external behaviors necessary for survival, including how the body responds to threats and processes pain.
Where the Periaqueductal Gray is Located
The periaqueductal gray is located in the midbrain, a part of the brainstem, surrounding the cerebral aqueduct, a channel that carries cerebrospinal fluid. This central position allows it to receive extensive input from brain regions above and send output to structures below in the spinal cord and lower brainstem.
The PAG is organized into several distinct columns that run longitudinally along its length. These columns—the dorsolateral, lateral, and ventrolateral regions—are defined by their unique connections and functions rather than clear physical boundaries. Each column handles different types of input and output, allowing the structure to manage a wide variety of bodily and behavioral responses.
The Central Hub for Pain Control
The periaqueductal gray is a primary regulator within the descending pain modulation system, the brain’s internal mechanism for controlling pain perception. When the body experiences a painful stimulus, the PAG receives ascending pain signals via the spinomesencephalic pathway from the spinal cord. It also receives input from forebrain regions, like the cortex, which provide emotional context about the pain.
In response, the PAG initiates a descending cascade to suppress the incoming pain signals. It projects to the rostroventral medulla (RVM), which then sends signals down to the dorsal horn of the spinal cord. This pathway effectively inhibits the transmission of nociceptive signals before they reach the brain for conscious processing.
This analgesia relies heavily on the body’s endogenous opioids, such as endorphins and enkephalins, produced by cells within the PAG. These opioids act on receptors in the PAG to activate the descending pain-blocking circuit. The RVM also releases neurotransmitters, including serotonin, which further suppresses signal transmission in the spinal cord.
This descending system is highly dynamic and influenced by emotional and psychological factors. Alterations in the balance of the PAG’s inhibitory and facilitatory functions are suspected to contribute to persistent chronic pain states. Targeting the PAG through methods like deep brain stimulation has been explored as a treatment option for severe, treatment-resistant chronic pain.
Orchestrating Fight, Flight, and Freeze
The PAG is the central command post for initiating immediate defensive behaviors in response to perceived threat. It translates sensory input about danger, often from the amygdala, into the “fight, flight, or freeze” survival responses, organized by its different columns.
The active defense responses, fight (aggressive confrontation) and flight (escape), are primarily mediated by the dorsolateral and lateral columns. Activation of these regions mobilizes the body for action, accompanied by sympathetic nervous system activation, increasing heart rate and blood pressure. This pattern maximizes the chance of escaping or warding off an immediate threat.
The passive defense response, freezing or immobility, is linked to the ventrolateral column. Freezing is a state of motor inhibition that occurs when active movement is deemed ineffective or too risky. During freezing, movement pauses while alertness remains high, serving as passive concealment.
The PAG couples these behavioral responses with appropriate physical changes, such as non-opioid mediated pain suppression during active defense. The selection of a specific response—active escape versus passive immobility—depends on the proximity and intensity of the threat.
Linking PAG to Emotional and Physiological States
The PAG’s role extends to regulating the emotional and physiological states that support survival behaviors. It acts on the autonomic nervous system to coordinate internal body changes accompanying emotional experiences. It strongly influences the cardiovascular system, adjusting heart rate and blood pressure in real-time to meet the demands of a defensive action.
These physiological outputs are organized by the same columnar structure that manages behavior, ensuring a cohesive body-wide response. For example, the ventrolateral PAG is associated with decreases in heart rate and blood pressure, often seen during passive coping or deep sleep.
The PAG also contributes to species-specific vocalization, such as distress calls or cries, which are forms of emotional communication. This function links the structure to fundamental aspects of social and emotional expression. By regulating these autonomic and expressive outputs, the PAG integrates emotion, behavior, and physiological well-being.