Periaqueductal gray matter

Endorphins are found primarily in the limbic system, hypothalamus, and brainstem. Enkephalins and dynorphin (in smaller quantities) are found primarily in the periaqueductal gray matter (PAG) of the midbrain, the limbic system, and the hypothalamus. These endogenous substances mimic the effects of morphine and other opiate drugs at many points in the analgesic system, including in the dorsal horns of the spinal cord. 

Figure 8.2 The endogenous analgesic system. The three major components of the endogenous analgesic system include the periaqueductal gray matter in the midbrain nucleus raphe magnus in the medulla and pain inhibitory complex in the dorsal horns of the spinal cord. This system causes presynaptic inhibition of pain fibers entering the spinal cord. The binding of enkephalin to opioid receptors on the pain fibers prevents release of the neurotransmitter, substance P. As a result, the pain signal is terminated in the spinal cord and does not ascend to higher centers in the CNS.

Lu J., Jhou T. C., Saper C. B. (2006). Identification of wake-active dopaminergic neurons in the ventral periaqueductal gray matter. J. Neurosci. 26(1), 193-202. 

Weber, RJ. and Pert, A., The periaqueductal gray matter mediates opiate-induced im-munosuppresion, Science, 245, 188, 1989. 

Llewelyn MB, Azami B, Grant CM, Roberts MHJ. (1981). Analgesia following microinjection of nicotine into the periaqueductal gray matter (PAG). Neurosci Lett. 7 S277. 

Herbert, H. and Saper, C. B. Organization of medullary adrenergic and noradrenergic projections to the periaqueductal gray matter in the rat, J. Comp. Neurol. 1992, 315, 34-52. 

Maione, S., Oliva, P., Marabese, I., Palazzo, E., Rossi, F., Berrino, L., Rossi, F., Filipelli, A. Periaqueductal gray matter metabotropic glutamate receptors modulate formalin-induced nociception, Pain 2000, 85, 183-189. 

In the suprachiasmatic and paraventricular nuclei VIP immunoreactivity increases during the dark period, when rodents are mostly awake, and decreases during the subsequent light period, when most of the time is spent in sleep (141,142). In addition, VIP immunoreactivity exhibits diurnal variations in the locus ceruleus nucleus and the periaqueductal gray matter. REM sleep depriva-... 

Sante AB, Nobre MJ, Brandao ML (2000) Place aversion induced by blockade of mu or activation of kappa opioid receptors in the dorsal periaqueductal gray matter. Behav Pharmacol 11 583-589... 

Prado WA, Pelegrini-da-Silva A, Martins AR (2003) Microinjection of renin-angiotensin system peptides in discrete sites within the rat periaqueductal gray matter elicits antinociception. Brain Res 972 207-215... 

Potency relative to methionine enkephalin receptor affinities obtained by binding studies with 3H-naloxone analgesic carried out in rats following peptide injection into brain periaqueductal gray matter. b The terminal carboxyl group is reduced to an alcohol function. c The sulfur atom of methionine is oxidized to sulfoxide ... 

Electrical stimulation of the periaqueductal gray matter has produced naloxone-reversible analgesia that displays cross-tolerance with morphine analgesia and releases endogenous opioid peptides into the CSF. Enkephalins also exist in cells whose functions relate to bowel motility (nerve plexuses and exocrine glands of the stomach and intestine). 

Opiate receptors (named for opium, a euphoric drug that acts at these receptors), are located along the periaqueductal gray matter. Morphine and related drugs act at opiate receptors to relieve pain (Table 3.7A, 3.7B). In times of stress or pain, endogenous peptides act at opiate receptors. 

Fig. 1.3 A cross-section through the mrdbrain that illustrates the tectum, tegmentum and peduncular regions. Within the wall of the midbrain, note the positions of the periaqueductal gray matter, red nucleus, medial lemniscus, substantia nigra, and territory occupied by the reticular formation. (HI nucleus of cranial nerve III, the oculomotor nerve) (See also Color Insert)...

Sander G, Dessort D, Schmidt P., and Karli P. (1981) Distribution of GABA in the periaqueductal gray matter. Effects of medial hypothalamus lesions. Brain Res 224, 279-280,... 

Jacquet, Y. F., and Lajtha, A., 1974, Paradoxical effects after microinjection of morphine in the periaqueductal gray matter of the rat. Science 185 1055-1057. 

Sakurada, O., Sokoloff, L., and Jacquet, Y. F., 1978, Local cerebral glucose utilization following injection of p-endorphin into periaqueductal gray matter in the rat. Brain Res. 153 403-407. 

Another important site of opioid-mediated analgesia is the periaqueductal gray matter. This area of brain, as noted above, is rich in opioid receptors, and exercises descending anti-nociceptive influence on the dorsal horn of the spinal cord. 

Perception of bitterness, 2265 Perfumes, 3289 Perhydropurine, 54 Perhydropurine alkaloid, 42 Periaqueductal gray matter, 1371 Pericardial fluid, 1082 Pericarpium papaveris, 1100 Peridinin, 3254, 3256, 3264 Peridroma saucia, 4095 Perigianduia... 

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