'Periaqueductal gray' (PAG; also called the "central gray") is the
midbrain grey matter that is located around the
cerebral aqueduct within the
midbrain. It plays a role in the descending modulation of
pain and in defensive behaviour. The ascending pain and temperature fibers of the
spinothalamic tract also send information to the PAG via the ''spinomesencephalic tract''. The spinomesencephalic tract is so-named because the fibers originate in the
spine and terminate in the
mesencephalon, another name for the midbrain, which is the part of the brain in which the PAG resides.
Role in Analgesia
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 gelitanosa). 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.
★ Three known kinds of opioid receptors have been identified- mu, kappa, and delta. Synthetic opioid and opioid-derivative drugs activate these receptors (possibly by acting on the PAG directly, where a dense amount of these receptors are expressed) to produce analgesia- including heroin, morphine, vicodin, and similar pain modulating compounds.
Role in defensive behavior
Stimulation of the dorsal and lateral aspects of the PAG [in the rat] can provoke defensive responses characterised by
freezing, running, jumping, tachycardia and increases in blood pressure and muscle tonus. Conversely, stimulation of the caudal ventrolateral PAG can result in an immobile, relaxed posture known as
quiescence.
Lesions of the caudal ventrolateral PAG can greatly reduce
conditioned freezing, while lesions of the dorsal aspect can reduce innate defensive behavior, virtually "taming" the animal.
Role in reproductive behavior
Neurons of the PAG are excited by
endorphins and by
opiate analgesics. It also plays a role in
female copulatory behavior (see
Lordosis behavior) via a pathway from the ventromedial nucleus of the
hypothalamus.
Additional images
External links
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