Medullary circuits for nociceptive modulation

Abstract

Neurons in the medullary raphe are critical to opioid analgesia through descending projections to the dorsal horn. Work in anesthetized rats led to the postulate that nociceptive suppression results from tonic activation of nociceptive-inhibiting neurons and tonic inhibition of nociceptive-facilitating neurons. However, morphine does not cause tonic changes in raphe neuronal firing in unanesthetized rodents. Recent work suggests that a drop in activity of nociceptive-inhibiting neurons synchronizes nociceptive circuits and a burst of activity in nociceptive-facilitating neurons facilitates withdrawal magnitude. After morphine, the phasic responses of raphe cells are suppressed along with nociceptive withdrawals. The results suggest a new model of brainstem modulation of nociception in which the medullary raphe facilitates nociceptive reactions when noxious input occurs and may modulate other functions between injurious events.

Loss of neurons in rostral ventromedial medulla that express neurokinin-1 receptors decreases the development of hyperalgesia

“…Pronociceptive and antinociceptive descending modulation from the RVM is mediated by activity of ON and OFF neurons, respectively (Fields et al, 1983; Fields and Heinricher, 1985; Mason, 2012). We have previously demonstrated that only ON cells were activated by iontophoretic application of an NK-1R agonist (Budai et al, 2007) suggesting that NK-1Rs are located mainly on subset of these pronociceptive neurons.…”

“…These cells are not affected by noxious cutaneous stimuli but may modulate nociceptive transmission of visceral (Brink and Mason, 2003, 2004; Brink et al, 2006) and trigeminal (Ellrich et al, 2000) inputs. Serotonergic cells are a separate group of RVM neurons defined by slow, regular discharge and distinct neurochemistry that appears to modulate autonomic activities (Potrebic et al, 1994; Mason, 1997, 2012). …”

Neuropathic pain-induced enhancement of spontaneous and pain-evoked neuronal activity in the periaqueductal gray that is attenuated by gabapentin

“…The ventrolateral periaqueductal gray (vlPAG) is an important brainstem structure, exerting both inhibitory and facilitatory effects on pain perception [22; 24; 30; 37; 38]. The vlPAG modulates spinal cord nociceptive transmission via projections to the rostral ventral medulla (RVM), forming the PAG-RVM-spinal descending pain inhibitory network [16; 22].…”

The coexistence of VGluT2 and neurotensin or leu-enkephalin in the medullary dorsal horn: A confocal and electron microscopic immunohistochemical study in the rat

“…The medullary dorsal horn (MDH) has been extensively investigated immunohistochemically in relation to the transmission, and modulation of orofacial nociceptive signals, especially lamina II [1,2]. Neurotensin (NT)-and enkephalin (ENK)-containing neurons, and nerve endings are present in the superficial layers of the MDH [3][4][5][6][7][8].…”