Tonic release of serotonin: A mechanism for antinociception?

Abstract

I n their Focus article, Mason and Gao question the long-held idea that morphine administration or electrical stimulation in the periaqueductal gray (PAG) excites descending bulbospinal serotonergic neurons in the raphe magnus (RM) and the adjacent nucleus reticular magnocellularis, and thus causes the release of serotonin (5-HT) from the terminals of these neurons in the dorsal horn and inhibition of nociceptive neurons in the spinal cord [2]. Although many physiologic and anatomic studies have shown that 5-HT modulates nociceptive transmission in the spinal cord, the correlation between PAG stimulation/morphine administration and the firing activity of 5-HT neurons in the RM has never been studied in detail. This gap in knowledge is addressed by a series of elegant studies by Mason and co-workers [6,7,19]. Recording from RM neurons and subsequently immunolabeling the cells, Mason has established a discriminant function to classify 5-HT neurons in the RM [19]. Because this method of classification gives less than 5% of error, one can, with a certain degree of confidence, use a set of physiologic criteria established by the discriminant function to identify 5-HT cells, thus avoiding laborious labeling of each recorded cell. Using this approach, Mason and colleagues have shown that 5-HT neurons in the RM fire slowly and steadily, resembling many 5-HT cells in other regions of the brain [13]. More interestingly, the discharge patterns of most RM 5-HT cells are hardly affected by noxious tail heat, paw or tail pinch, and tail-flick withdrawal [19]. Furthermore, most 5-HT cells do not respond to PAG stimulation or by morphine administration, even though some 5-HT neurons are inhibited or excited by these manipulations [6,7]. In those 5-HT cells that are excited