Evidence for pain modulation by pre- and postsynaptic noradrenergic receptors in the medulla oblongata.
Activation of neurons in nucleus raphe magnus (NRM) produces hypoalgesia which most likely results from inhibition of spinal cord pain transmission pathways. Previous reports from this laboratory suggest that noradrenergic (NA) neurons modulate the activity of NRM neurons. More specifically, NA projections to NRM neurons appear to be inhibitory since iontophoretically applied norepinephrine (NE) inhibits the activity of NRM neurons. Furthermore, blockade of NA receptors in the NRM by the microinjection of alpha-adrenergic antagonists produces potent analgesia. Thus, the NA input to the NRM appears to increase pain sensitivity by tonically inhibiting NRM neurons. Pharmacological and physiological studies have differentiated alpha-adrenergic receptors into alpha-1 and alpha-2 subtypes. The present study was designed to examine the nature of the alpha-adrenergic receptor subtypes in the NRM and their role in the modulation of pain sensitivity. The results of these experiments are consistent with the classical model of postsynaptic alpha-1 receptors and presynaptic alpha-2 receptors which modulate NE release. Both the alpha-1 antagonist, prazosin, and the alpha-2 agonist, clonidine, produced an increase in nociceptive threshold. Conversely, both the alpha-1 agonist, phenylephrine, and the alpha-2 antagonist, yohimbine, produced a decrease in nociceptive threshold. Thus, in the region of the NRM, both presynaptic alpha-2 and postsynaptic alpha-1 noradrenergic receptors may be involved in the modulation of nociception.
Sagen
J
J
Proudfit
H K
HK
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001931:Brain Mapping; D005260:Female; D009638:Norepinephrine / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000503:physiopathology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000503:physiopathology*; D012684:Sensory Thresholds; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine