There is a body of evidence implicating the neurons of the rostral ventral medulla (RVM) in modulation of pain and, particularly, in mediating the analgesic effects of systemically administered opiate drugs such as morphine. Endogenous opioid peptide-containing neurons and terminals are present not only within RVM but are also present in other CNS sites that project to and receive projections from the RVM. In addition to enkephalin, there is evidence that serotonin, noradrenalin and other putative neurotransmitters are present in nerve terminals in RVM. Our goal is to elucidate the internal circuitry and function of RVM, particularly the role of opioid peptides. The strategy is to define RVM neuron cell classes on the basis of their receptive field and relationship of their discharge to nocifensive behavior. We will then map the location of each class and determine whether cells of that class project to the spinal cord. The effect on each class of either systemically injected or iontophoresed opiates will then be studied. Using intracellular marking of single RVM cells and double-labelling we plan to determine whether particular physiologically defined classes of cell contain particular transmitters or receive input from cells containing particular transmitters. We will use cross-correlation analysis to study connectivity between simultaneously recorded pairs of cells in RVM. In addition to better understanding of pain-modulating networks in the CNS, these studies, by defining the roles of both opioid and non-opioid neurons may suggest new classes of centrally-acting analgesic drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA001949-10
Application #
3207050
Study Section
(DABA)
Project Start
1978-02-01
Project End
1989-01-31
Budget Start
1987-02-01
Budget End
1988-01-31
Support Year
10
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Yun, I A; Fields, H L (2003) Basolateral amygdala lesions impair both cue- and cocaine-induced reinstatement in animals trained on a discriminative stimulus task. Neuroscience 121:747-57
Heinricher, M M; Morgan, M M; Tortorici, V et al. (1994) Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla. Neuroscience 63:279-88
Clarke, R W; Morgan, M M; Heinricher, M M (1994) Identification of nocifensor reflex-related neurons in the rostroventromedial medulla of decerebrated rats. Brain Res 636:169-74
Morgan, M M; Heinricher, M M; Fields, H L (1994) Inhibition and facilitation of different nocifensor reflexes by spatially remote noxious stimuli. J Neurophysiol 72:1152-60
Morgan, M M; Fields, H L (1993) Activity of nociceptive modulatory neurons in the rostral ventromedial medulla associated with volume expansion-induced antinociception. Pain 52:1-9
Levine, J D; Fields, H L; Basbaum, A I (1993) Peptides and the primary afferent nociceptor. J Neurosci 13:2273-86
Fields, H L; Heinricher, M M; Mason, P (1991) Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 14:219-45
Heinricher, M M; Drasner, K (1991) Lumbar intrathecal morphine alters activity of putative nociceptive modulatory neurons in rostral ventromedial medulla. Brain Res 549:338-41
Kaplan, H; Fields, H L (1991) Hyperalgesia during acute opioid abstinence: evidence for a nociceptive facilitating function of the rostral ventromedial medulla. J Neurosci 11:1433-9
Haws, C M; Heinricher, M M; Fields, H L (1990) Alpha-adrenergic receptor agonists, but not antagonists, alter the tail-flick latency when microinjected into the rostral ventromedial medulla of the lightly anesthetized rat. Brain Res 533:192-5

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