title: Projections from the mesopontine tegmental anesthesia area to regions involved in pain modulation.
abstract: Pentobarbital microinjected into a restricted locus in the upper brainstem induces a general anesthesia-like state characterized by atonia, loss of consciousness, and pain suppression as assessed by loss of nocifensive response to noxious stimuli. This locus is the mesopontine tegmental anesthesia area (MPTA). Although anesthetic agents directly influence spinal cord nociceptive processing, antinociception during intracerebral microinjection indicates that they can also act supraspinally. Using neuroanatomical tracing methods we show that the MPTA has multiple descending projections to brainstem and spinal areas associated with pain modulation. Most prominent is a massive projection to the rostromedial medulla, a nodal region for descending pain modulation. Together with the periaqueductal gray (PAG), the MPTA is the major mesopontine input to this region. Less dense projections target the PAG, the locus coeruleus and pericoerulear areas, and dorsal and ventral reticular nuclei of the caudal medulla. The MPTA also has modest direct projections to the trigeminal nuclear complex and to superficial layers of the dorsal horn. Double anterograde and retrograde labeling at the light and electron microscopic levels shows that MPTA neurons with descending projections synapse directly on spinally projecting cells of rostromedial medulla. The prominence of the MPTA's projection to the rostromedial medulla suggests that, like the PAG, it may exert antinociceptive actions via this bulbospinal relay.
authors.affiliation: Department of Cell and Animal Biology, Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem 91904, Israel. sinna@vms.huji.ac.il
authors.forename: I
authors.initials: I
authors.lastname: Sukhotinsky
authors.forename: K
authors.initials: K
authors.lastname: Reiner
authors.forename: R
authors.initials: R
authors.lastname: Govrin-Lippmann
authors.forename: M
authors.initials: M
authors.lastname: Belenky
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.forename: D A
authors.initials: DA
authors.lastname: Hopkins
authors.forename: C B
authors.initials: CB
authors.lastname: Saper
authors.forename: M
authors.initials: M
authors.lastname: Devor
mesh_terms: D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives; D001931:Brain Mapping; D002772:Cholera Toxin; D003911:Dextrans; D004525:Efferent Pathways / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D008297:Male; D046529:Microscopy, Electron, Transmission; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D011149:Pons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012154:Reticular Formation / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: D000777:Anesthetics; D003911:Dextrans; C076397:biotinylated dextran amine; D049452:Green Fluorescent Proteins; D001710:Biotin; D002772:Cholera Toxin