Delta opioid receptor mediated actions in the rostral ventromedial medulla on tail flick latency and nociceptive modulatory neurons.
The rostral ventromedial medulla (RVM) is critical for the modulation of dorsal horn nociceptive transmission. Three classes of RVM neurons (ON, OFF, and NEUTRAL) have been described that have distinct responses to noxious stimuli and mu opioid receptor (MOR) agonists. The present study in barbiturate anesthetized rats investigated the effects of the delta 2 opioid receptor (DOR2) agonist, [D-Ala2]deltorphin II (DELT), microinfused into the RVM on the tail flick reflex and activity of RVM neurons. Tail flick latencies increased dose-dependently after administration of DELT (0.6 nmol and 1.2 nmol). Furthermore, DELT inhibited the tail flick related increase in ON cell activity and shortened the tail flick related pause in OFF cell activity. The activity of NEUTRAL cells was not affected. The antinociceptive effects and corresponding changes in ON and OFF cell activity produced by DELT were antagonized by the DOR2 antagonist, naltriben methanesulfonate, administered at the same site. These DOR2 mediated effects on noxious stimulation-evoked changes in RVM neuronal activity are similar to those reported for MOR agonists and suggest that both DOR2 and MOR produce analgesia through activation of OFF cells.
Harasawa
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Department of Neurology and the W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, USA.
Fields
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Meng
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ID
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
C000593231:DOR2 protein, rat; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone