The?periaqueductal gray?(PAG, also known as the?central gray) is a?nucleus?that plays a critical role in?autonomic?function,?motivated?behavior and behavioural responses to threatening stimuli.[1][2]?PAG is also 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.

Role in analgesia[edit]

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?and?kappa 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.（這里面不包括溫度感覺信息。）?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.[3]?The periaqueductal gray is also activated by viewing distressing images associated with pain.[4]

Three known kinds of?opioid receptors?have been identified:?mu (μ),?kappa (κ)?and?delta (δ). Synthetic opioid and opioid-derivative drugs activate these receptors (possibly by acting on the PAG directly, where these receptors are densely expressed) to produce analgesia.?These drugs include?morphine,?heroin?(diacetylmorphine),?pethidine,?hydrocodone,?oxycodone, and similar pain-reducing compounds.

Role in defensive behavior[edit]

Dorsal PAG neurons are activated during various defensive behaviors.[5]?Stimulation of the dorsal and lateral aspects of the PAG?can provoke defensive responses characterised by freezing immobility, running, jumping,?tachycardia, and increases in blood pressure and?muscle tonus. In contrast, stimulation of the caudal ventrolateral PAG?can result in an immobile, relaxed posture known as?quiescence, whereas its inhibition leads to increased locomotor activity.

(來自layer1附近的疼痛信息（如下圖所示）投射到caudal PAG，是不是意味著這類疼痛信息導(dǎo)致的行為是變軟弱，同時(shí)這類疼痛信息投射到caudal VTA，從而激發(fā)DA system，這是不是互相逗鬧狀態(tài)下造成的疼痛，逗鬧是大家都喜歡的，是一種輕度的疼痛，畢竟你打別人，你自己也是同樣要疼的。)

?

Lesions of the caudal ventrolateral PAG can greatly reduce?conditioned?freezing, whereas lesions of the dorsal aspect can reduce innate defensive behavior, virtually "taming" the animal[citation needed].

Role in reproductive behavior[edit]

Neurons?of the PAG are excited by?endorphins?and by?opiate?analgesics

(這句話存在問題，endorphins?and?opiate屬于opioid，其受體是G蛋白偶聯(lián)受體，且是促代謝降低型的，endorphins?and?opiate與受體結(jié)合的直接效果是抑制，按理說Neurons?of the PAG應(yīng)該是被抑制的呀，從而降低交感系統(tǒng)的活動(dòng)。但是如果PAG包含兩個(gè)部分，dorsal and lateral aspects of the PAG（憤怒部分）和the caudal ventrolateral PAG（放松部分），那么會(huì)不會(huì)是這樣，endorphins?and?opiate抑制了憤怒部分，從而興奮了放松部分？

Lordosis這種脊柱的彎曲姿勢對應(yīng)著NE與serotonin濃度同時(shí)在spinal cord中釋放，同時(shí)會(huì)有自信的感受，而負(fù)責(zé)satiety感受的ventromedial nucleus of the?hypothalamus的活動(dòng)也對應(yīng)著serotonin在該核團(tuán)處釋放。好像人在抻懶腰的時(shí)候也出現(xiàn)Lordosis姿勢，或許此時(shí)是憤怒部分與放松部分同時(shí)活動(dòng)吧。問題時(shí)，orbitofrontal cortex可以直接投射到PAG，且能產(chǎn)生pleasantness，那這里一定是去興奮放松部分，很有可能是通過orbitofrontal cortex-occipital cortex-temporal cortex-orbitofrontal cortex這樣的路徑來通過視覺信息產(chǎn)生pleasantness。所以對于憤怒與pleasantness

的情緒，是可以通過主觀意識進(jìn)行隨意控制的?？傊?，目前來看PAG的重要性提升到與interpeduncular nucleus同樣重要的程度。PAG活動(dòng)導(dǎo)致交感系統(tǒng)興奮的原因是：PAG抑制了interpeduncular nucleus，從而不讓interpeduncular nucleus抑制兩側(cè)的DA系統(tǒng)，而VTA投射到杏仁核興奮之，杏仁核再投射到PAG興奮之，會(huì)進(jìn)一步讓interpeduncular nucleus被抑制，從而讓多巴胺更加不被抑制，這就是憤怒情緒對應(yīng)著多巴胺的強(qiáng)烈釋放。)

. It also plays a role in?female?copulatory behavior?(see?lordosis behavior) via a pathway from the ventromedial nucleus of the?hypothalamus.

Role in maternal behavior[edit]

The PAG may be specifically involved in human?maternal behavior. The PAG contains a high density of?vasopressin?and?oxytocin?receptors, and it has direct connections with the?orbitofrontal cortex

（oxytocin對PAG、amygdala的作用是降低PAG的功能，從而降低交感系統(tǒng)被PAG興奮的程度，這樣一來自然副交感系統(tǒng)就要上位，那么此時(shí)再通過nucleus accumbens來抑制副交感系統(tǒng)從而允許交感系統(tǒng)興奮，這樣人的行為特征就是溫柔和善，充滿母愛。對于男的也一樣，oxytocin與腦內(nèi)的受體結(jié)合最終效果就是降低NE濃度和PAG的工作強(qiáng)度。但是oxytocin并不降低PAG投射raphe magnus的能力，所以此時(shí)的人不怕疼，PAG可以通過多巴胺系統(tǒng)來興奮，但是暴怒行為特點(diǎn)是近似不理智的瘋狂，且無法對自己的幼崽兒暴怒。換句話說，是外界信息通過大腦皮層最終激發(fā)了oxytocin的釋放，而這個(gè)外界信息，對于父親母親來說，是孩子，這一點(diǎn)十分清楚；非親子關(guān)系的，那個(gè)能激發(fā)人的oxytocin釋放的外界信息，這個(gè)人是沒辦法對這個(gè)外界信息產(chǎn)生“怒”的，但是會(huì)對那些傷害這個(gè)外界信息的東西暴怒。所以，通過這一條定理，是可以判斷某個(gè)人是否處于oxytocin濃度高狀態(tài)，他/她對誰產(chǎn)生了高oxytocin濃度維持。而且是要通過行為來維持oxytocin，比如耐心地喂孩子吃飯的過程，就是oxytocin高濃度釋放的過程，總之就是那些能讓交感系統(tǒng)不興奮而通過nucleus accumbens來抑制副交感系統(tǒng)的行為。簡單來說，就是人對某個(gè)對象產(chǎn)生行為，在產(chǎn)生這個(gè)行為的過程中，oxytocin在被釋放，所謂的感情上的親近感，你對有親近感的人或物，僅僅是看上幾眼就能讓你產(chǎn)生oxytocin。Vasopressin對PAG、amygdala起的作用應(yīng)該類似，也是降低其工作狀態(tài)，但是相反的是是通過提高serotonin濃度來實(shí)現(xiàn)，處于vasopressin狀態(tài)下的人應(yīng)該是處于規(guī)則行為狀態(tài)，對他人有好感，因而不暴怒，會(huì)對那些傷害他的有好感人的人暴怒。這樣的高vasopressin濃度的人也是不理智的，顯現(xiàn)出偏執(zhí)的特點(diǎn)。那些年輕的男孩不會(huì)談戀愛，在愛情中對某事物顯得偏執(zhí)，應(yīng)該是處于vasopressin高濃度狀態(tài)，等到他能夠裝變?yōu)閛xytocin高濃度狀態(tài)時(shí)，他才不會(huì)那么盛氣，會(huì)溫柔下來吧。顯然高vasopressin狀態(tài)的男孩要比高oxytocin狀態(tài)的男孩身體更強(qiáng)壯，但是情商更低得多。）

, which might mediate the role of the PAG in maternal love. The lateral orbitofrontal cortex is activated by pleasant visual, tactile, and olfactory stimuli. Its response depends on pleasantness rather than on intensity of stimulation. Here, its activity is likely to reflect one aspect of the pleasant emotions associated with motherly love.[6]