Potential Role of Medullary Raphe-Spinal Neurons in Cutaneous Vasoconstriction: An In Vivo Electrophysiological Study

Abstract

Nalivaiko, Eugene and William W. Blessing. Potential role of medullary raphe-spinal neurons in cutaneous vasoconstriction: an in vivo electrophysiological study. J Neurophysiol 87: 901-911, 2002; 10.1152/jn.00221.2001. In rabbits, raphe magnus/pallidus neurons form a link in the CNS pathway regulating changes in cutaneous blood flow elicited by nociceptive stimulation and activation of the central nucleus of the amygdala. To characterize relevant raphe-spinal neurons, we performed extracellular recordings from the rostral medullary raphe nuclei in anesthetized, paralyzed, mechanically ventilated rabbits. All studied neurons were antidromically activated from the dorsolateral funiculus of the spinal cord (C 8 -T 2 ). Of 129 studied neurons, 40% were silent. The remaining neurons discharged spontaneously at 0.3-29 Hz. Nociceptive stimulation (lip squeeze with pliers) excited 63 (49%), inhibited 9 (7%), and did not affect 57 (44%) neurons. The same stimulation also elicited falls in ear pinna blood flow. In neurons activated by the stimulation, the increase in discharge preceded the fall in flow. Electrical stimulation of the spinal trigeminal tract excited 61/63 nociception-activated neurons [onset latencies range: 6 -75 ms, mean: 28 Ϯ 3 (SE) ms], inhibited 9/9 nociceptioninhibited neurons (onset latencies range: 9 -85 ms, mean: 32 Ϯ 10 ms), and failed to affect 55/57 neurons insensitive to nociceptive stimulation. Neurons insensitive to nociceptive/trigeminal stimulation were also insensitive to nonnociceptive tactile stimulation and to electrical stimulation of the amygdala. They were either silent (32/45) or discharged regularly at low frequencies. They possessed longduration action potentials (1.26 Ϯ 0.08 ms) and slow-conducting axons (6.0 Ϯ 0.5 m/s). These neurons may be serotonergic raphespinal cells. They do not appear to be involved in nociceptive-related cutaneous vascular control. Of the 63 neurons sensitive to nociceptive and trigeminal tract stimulation, 35 also responded to tactile stimulation (wide receptive field). These neurons possessed short action potentials (0.80 Ϯ 0.03 ms) and fast-conducting axons (30.3 Ϯ 3.1 m/s). In this subpopulation, electrical stimulation of the amygdala activated nearly all neurons tested (10/12), with a mean onset latency of 34 Ϯ 3 ms. The remaining 28 neurons sensitive to nociceptive and trigeminal stimulation did not respond to tactile stimuli and were mainly unaffected by amygdala stimulation. It may be that fastconducting raphe-spinal neurons, with wide multimodal receptive fields and with input from the central nucleus of the amygdala, constitute the bulbo-spinal link in the CNS pathway regulating cutaneous blood flow in response to nociceptive and alerting stimuli.

Involvement of medullary serotonergic groups in multiple system atrophy

“…6 Thus, serotonergic inputs may influence sympathetic outflow both at medullary and spinal levels. The rostral medullary raphe, including the RPa and RMg, controls sympathetic outflow to the brown fat 5 and skin blood vessels 3,4 and has been implicated in thermoregulatory responses to cold stimuli, as well as skin vasoconstrictor responses to pain or amygdala stimulation. 4 Although…”

“…2 Likewise, in patients with cystic fibrosis resulting from premature stop codon mutations in the CFTR gene, treatment with gentamicin resulted in increased CFTR expression and chloride conductance across the nasal epithelium. [3][4][5] Despite these encouraging results, two clinical trials of gentamicin treatment in DMD have observed no changes in muscle strength or increased dystrophin…”

“…1 Serotonergic neurons of the nucleus raphe pallidus (RPa), raphe obscurus (ROb), raphe magnus (RMg), and ventrolateral medullary reticular formation (VLM) project to the intermediolateral cell column. 2 The rostral medullary raphe selectively regulates sympathetic discharge to cutaneous vessels 3,4 and brown fat 5 and thus may be involved in thermoregulatory responses. Although not all bulbospinal raphe neurons contain serotonin, serotonergic projections from these regions may exert complex effects on sympathetic preganglionic neurons, both directly 6 or via influence on vasomotor neurons of the rostral VLM.…”

Activation of slowly conducting medullary raphé-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit

“…In that study, we antidromically activated medullary raphé-spinal neurons and examined the subclass of cells activated by electrical stimulation of the trigeminal tract (a procedure that vigorously constricts the ear pinna bed). The discharge of raphé-spinal neurons with axonal conduction velocities as high as 30 m/s was substantially increased by this procedure (34). The pathway from the trigeminal tract to the spinal cord is presumably exclusively via the raphé, since inactivation of this region with muscimol entirely abolishes trigeminally elicited increases in sympathetic cutaneous vasomotor discharge (7,40).…”

Cutis Marmorata skin decompression sickness is a manifestation of brainstem bubble embolization, not of local skin bubbles

“…The autonomic regulation of skin microcirculation is a highly complex and integrated process, whose ''driving neurons" are located in the brainstem, more specifically in the rostral ventromedial medulla, close to the integrative area called ''formatio reticularis" [22][23][24]. One of the most important functions of skin microcirculation appears to be its role in thermoregulation: by dilatation or constriction they allow for a rather efficient heat dissipation [25].…”