The antinociception produced by microinjection of a cholinergic agonist in the ventromedial medulla is mediated by noradrenergic neurons in the A7 catecholamine cell group
Abstract
Activation of neurons in the ventromedial medulla by electrical stimulation or by microinjection of opioid or cholinergic agonists produces antinociception that is mediated in part by spinally-projecting noradrenergic neurons. Several lines of evidence indicate that these noradrenergic neurons are located in the pontine A7 catecholamine cell group. For example, anatomical studies have demonstrated that neurons in the ventromedial medulla project to the noradrenergic neurons in the A7 catecholamine cell group that provide the major noradrenergic innervation of the spinal cord dorsal horn. In addition, electrical and chemical stimulation of A7 neurons produces antinociception that can be reduced by intrathecal injection of alpha2-adrenoceptor antagonists. The present studies provide more direct evidence that activation of neurons in the ventromedial medulla produces antinociception by activating noradrenergic neurons in the A7 cell group. Neurons in the ventromedial medulla were stimulated by microinjecting the cholinergic agonist carbachol (5 microg) into sites in the nucleus raphe magnus or the nucleus gigantocellularis pars alpha of pentobarbital anesthetized Sprague-Dawley rats. In some experiments, the local anesthetic tetracaine (10 microg) was then microinjected near the A7 cell group to inactivate the spinally-projecting noradrenergic neurons. In other experiments, cobalt chloride (100 mM) was microinjected near the A7 cell group to block synaptic activation of spinally…
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Non-opioid analgesia accompanies the active defense responses (flight or fight), and opioid analgesia accompanies the passive defense responses (freezing, tonic immobility, collapsed immobility, and quiescent immobility).
“Non-opioid analgesia accompanies the “active” defense responses (flight or fight), and opioid analgesia accompanies the “passive” defense responses (freezing, tonic immobility, collapsed immobility, and quiescent immobility).28–30”
From Fear and the Defense Cascade (2015) · cites this paper as [30]
The order of the human defense cascade differs from conceptualizations based on the distance of the predatory threat, in which freezing is discussed before flight or fight.
“This order differs from conceptualizations based on the distance of the predatory threat—in which freezing is discussed before flight or fight.2,8,9,17”
From Fear and the Defense Cascade (2015) · cites this paper as [17]
Flight or fight involves non-opioid analgesia, which can be evoked by activation of the LPAG, and projections to the spinal cord block ascending pain signals.
“Flight or fight involves non-opioid analgesia,28,29 which can be evoked by activation of the LPAG.28 Projections to the spinal cord block ascending pain signals.30”
From Fear and the Defense Cascade (2015) · cites this paper as [30]
Depending on the degree of threat and the distance between predator and prey, distinct animal defense responses-freezing, flight or fight, tonic immobility, and quiescent immobility-proceed sequentially along a continuum termed the defense cascade.
“Subsequent research with animals determined that, depending on the degree of threat and the distance between the predator and prey, distinct responses—freezing, flight or fight, tonic immobility, and quiescent immobility—proceed sequentially along a continuum, termed the defense cascade.”
From Fear and the Defense Cascade (2015) · cites this paper as [17]
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Kozlowska, K., Walker, P., McLean, L., & Carrive, P. (2015) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000065 · Cited by 468 · see citing works
“Projections to the spinal cord block ascending pain signals.(30)”
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Terpou, B. A., Harricharan, S., McKinnon, M. C., Frewen, P., Jetly, R., & Lanius, R. A. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24447 · Cited by 82 · see citing works
da Silva, L. F. S., Coimbra, N. C., & Menescal-de-Oliveira, L. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.05.020 · Cited by 11 · see citing works
- Authors
- Nuseir, K., Heidenreich, B. A., & Proudfit, H. K.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Proudfit, Herbert K.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 822
- Issue
- 1-2
- Pages
- 1-7
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W1979722034
- Cited by
- 46
- References
- 0
- Citations by year
- 2024: 2 · 2022: 1 · 2019: 1 · 2018: 1 · 2016: 1 · 2015: 2 · 2013: 1 · 2012: 3
- FWCI
- 2.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service
- National Institute on Drug Abuse (DA03980, R01DA003980)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- antinociception, ventromedial medulla, noradrenergic neurons, cholinergic agonists, carbachol, nucleus gigantocellularis, nucleus raphe magnus, spinally projecting neurons, dorsal horn, cobalt chloride, alpha2-adrenoceptors
- MeSH terms
- Anesthetics, Local, Animals, Carbachol, Cobalt, Female, Medulla Oblongata, Microinjections, Neurons, Afferent, Nociceptors, Norepinephrine, Pain, Pons, Raphe Nuclei, Tetracaine, Antimutagenic Agents, Rats, Sprague-Dawley, Receptors, Adrenergic, alpha-2, Cholinergic Agonists, Rats
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