Periaqueductal gray

Periaqueductal gray
Section through superior colliculus showing path of oculomotor nerve. Periaqueductal gray is the gray area just peripheral to the cerebral aqueduct.
Transverse section through mid-brain. Corpora quadrigemina Cerebral aqueduct Central gray stratum Interpeduncular space Sulcus lateralis Substantia nigra Red nucleus of tegmentum Oculomotor nerve, with 8’, its nucleus of origin Lemniscus (in blue) with a’ the medial lemniscus and a" the lateral lemniscus Medial longitudinal fasciculus Raphé Temporopontine fibers Portion of medial lemniscus, which runs to the lentiform nucleus and insula Cerebrospinal fibers Frontopontine fibers
Details
Identifiers
Latin	Substantia grisea centralis
MeSH	A08.186.211.132.659.822.595
NeuroNames	hier-501
NeuroLex ID	Periaqueductal gray
TA	A14.1.06.321
FMA	83134
Anatomical terms of neuroanatomy []

The periaqueductal gray (PAG) (also known as the central gray) is the primary control center for descending pain modulation. It has enkephalin-producing cells that suppress pain.

The periaqueductal gray is the gray matter located around the cerebral aqueduct within the tegmentum of the midbrain. It projects to the nucleus raphe magnus, and also contains descending autonomic tracts. The ascending pain and temperature fibers of the spinothalamic tract send information to the PAG via the spinomesencephalic tract (so-named because the fibers originate in the spine and terminate in the PAG, in the mesencephalon or midbrain).

This region has been used as the target for brain-stimulating implants in patients with chronic pain.

Stimulation of the periaqueductal gray matter of the midbrain activates enkephalin-releasing neurons that project to the raphe nuclei in the brainstem. 5-HT (serotonin) released from the raphe nuclei descends to the dorsal horn of the spinal cord where it forms excitatory connections with the "inhibitory interneurons" located in Laminae II (aka the substantia gelatinosa). When activated, these interneurons release either enkephalin or dynorphin (endogenous opioid neurotransmitters), which bind to mu opioid receptors on the axons of incoming C and A-delta fibers carrying pain signals from nociceptors activated in the periphery. The activation of the mu-opioid receptor inhibits the release of substance P from these incoming first-order neurons and, in turn, inhibits the activation of the second-order neuron that is responsible for transmitting the pain signal up the spinothalamic tract to the ventroposteriolateral nucleus (VPL) of the thalamus. The nociceptive signal was inhibited before it was able to reach the cortical areas that interpret the signal as "pain" (such as the anterior cingulate). This is sometimes referred to as the Gate control theory of pain and is supported by the fact that electrical stimulation of the PAG results in immediate and profound analgesia. The periaqueductal gray is also activated by viewing distressing images associated with pain.