Role of neurotensin in the nucleus raphe magnus in opioid-induced antinociception from the periaqueductal gray.
These studies examined the role of the neurotensinergic projections extending from the periaqueductal gray (PAG) to the nucleus raphe magnus (NRM) on the inhibition of the tail-flick reflex produced by microinjection of morphine or beta-endorphin in the PAG. Neurotensin (3-30 nmol) or the partial agonist [D-Trp11] neurotensin (100 and 300 pmol) microinjected into the NRM of awake rats produced a dose-dependent inhibition of the tail-flick response lasting 90 to 150 min. Lower doses of neurotensin (0.03-0.3 nmol) produced a hyperreflexive tail-flick response 10 min after injection, which correlated with a decreased hot plate latency. Additionally, a dose of [D-Trp11]neurotensin (3 pmol) that had no intrinsic activity antagonized both the antinociceptive as well as hyperreflexive responses of neurotensin. Morphine (6 nmol) injected into the PAG produced an inhibition of the tail-flick response that was enhanced by injection of [D-Trp11]neurotensin (3 pmol) into the NRM. In contrast, injection of [D-Trp11]neurotensin (3 pmol) into the NRM had no effect on the inhibition of the tail-flick produced by beta-endorphin (10 nmol) in the PAG. Antineurotensin antiserum yielded results similar to those obtained with [D-Trp11]neurotensin. Although neurotensin was found to produce changes in tail skin temperature, it was possible to dissociate these effects from changes in tail-flick latency. These data suggest that neurotensin produces both antinociceptive and hyperalgesic responses when injected into the NRM.(ABSTRACT TRUNCATED AT 250 WORDS)
Urban
M O
MO
Department of Anesthesiology, West Virginia University, Morgantown.
Smith
D J
DJ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects; D010487:Periaqueductal Gray / Q000187:drug effects / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D001615:beta-Endorphin / Q000494:pharmacology*
D000700:Analgesics; D009496:Neurotensin; D001615:beta-Endorphin; C024309:neurotensin, Trp(11)-; D009020:Morphine