Periaqueductal gray

AD= : Alzheimer disease; DBS= : deep brain stimulation; GABA= : γ-aminobutyric acid; NO= : nitric oxide; PAG= : periaqueductal gray; PVG= : periventricular gray matter; RVM= : rostral ventromedial medulla; TRPV1= : transient receptor potential vanilloid type 1; VLM= : ventrolateral medulla The periaqueductal gray (PAG) is an anatomic and functional interface between the forebrain and the lower brainstem and has a major role in integrated behavioral responses to internal (e.g., pain) or external (e.g., threat) stressors. The PAG consists of distinct columns that receive selective inputs from the prefrontal cortex, amygdala, hypothalamus, and nociceptive pathways. Via its connections with different brainstem nuclei, the PAG coordinates specific patterns of cardiovascular, respiratory, motor, and pain modulatory responses. These responses vary according to the type of stress and the subject's perception of the threatening stimulus. The PAG is also involved in vocalization, micturition, and thermoregulation, and contributes to mechanisms of arousal and control of REM sleep. The PAG is affected in neurodegenerative disorders, such as Alzheimer disease (AD) and multiple system atrophy. Stimulation of the PAG has been utilized for management of chronic neuropathic pain and recent evidence suggests that it may also be used to relieve refractory hypertension. The organization of the PAG and its multiple functions have been the subjects of several reviews.1,–,11 ### Anatomic subdivisions and neurochemistry. The PAG is continuous with the periventricular gray matter (PVG) and surrounds the midbrain aqueduct except for ventral part, which contains oculomotor-related nuclei rostrally and the dorsal raphe nucleus caudally (figure). Based on cytoarchitecture, chemoarchitecture, and connectivity patterns, the PAG has been subdivided into 4 columns: dorsomedial, dorsolateral, lateral, and ventrolateral.2,–,5 The PAG contains different types of neurons that utilize l-glutamate, γ-aminobutyric acid (GABA), opioids (particularly enkephalin), substance P, neurotensin, and other neurotransmitters. The dorsolateral PAG also contains neurons that express NADPH-diaphorase and synthesize nitric oxide (NO)12; the ventrolateral PAG contains a group of dopaminergic neurons.13 There is also abundant expression of NMDA,14 GABAA,15 μ-opioid,16 neurokinin-1,17 and transient receptor …