Vagal modulation of nociception is mediated by adrenomedullary epinephrine in the rat
Open accessAbstract
Vagal afferent activity modulates mechanical nociceptive threshold and inflammatory mediator‐induced hyperalgesia, effects that are mediated by the adrenal medulla. To evaluate the role of epinephrine, the major hormone released from the adrenal medulla, the β 2‐adrenergic receptor antagonist ICI 118,551 was chronically administered to vagotomized rats and epinephrine to normal rats. In vagotomized rats, chronic administration of ICI 118,551 markedly attenuated vagotomy‐induced enhancement of bradykinin hyperalgesia but had no effect on nociceptive threshold. In normal rats, chronic epinephrine had the opposite effect, enhancing bradykinin hyperalgesia. Like vagotomy‐, epinephrine‐induced enhancement of hyperalgesia developed slowly, taking 14 days to reach its peak. Vagotomy induced a chronic elevation in plasma concentrations of epinephrine. We suggest that ongoing activity in vagal afferents inhibits the release of epinephrine from the adrenal medulla. Chronically elevated levels of epinephrine, occurring after vagotomy, desensitize peripheral β 2‐adrenergic receptors and lead to enhancement of bradykinin hyperalgesia. The ability of prolonged elevated plasma levels of epinephrine to sensitize bradykinin receptors could contribute to chronic generalized pain syndromes.
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In rodents, vagotomy increases plasma epinephrine concentrations at baseline and after immobilization stress.
“and increased epinephrine concentrations in plasma at baseline and after immobilization stress (Khasar et al., 2003;Mravec et al., 2015).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Khasar et al., 2003
The Plasma epinephrine section reports higher plasma epinephrine in vagotomized rats than in sham-vagotomized rats at 3, 7, and 14 days after surgery, supporting the baseline portion. The paper does not report epinephrine measurements after immobilization stress in vagotomized rats; its Discussion mentions stress-related catecholamine elevations only in general. Page numbers were not available in our copy. (LLM, conf=0.88)
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Davis, M. C., Zautra, A. J., & Reich, J. W. (2001) · Annals of Behavioral Medicine · doi:10.1207/s15324796abm2303_9 · Cited by 189 · see citing works
Autonomic responses to stress in Vietnam combat veterans with posttraumatic stress disorder
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
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- Authors
- G. Khasar, S., G. Green, P., Miao, F. J. ‐., & Levine, J. D.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Levine, Jon D.
- ORCID
- Levine, Jon D.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2003-02
- Volume
- 17
- Issue
- 4
- Pages
- 909-915
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2075886029
- Cited by
- 107
- References
- 3
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 5 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 7 · 2014: 7 · 2013: 9 · 2012: 2
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01nr004880-05)
- National Institute of Nursing Research (NR004880)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- vagal afferents, epinephrine, adrenal medulla, beta2-adrenergic receptor, inflammatory hyperalgesia, mechanical nociceptive threshold, vagotomy, ICI 118,551, sympathetic nervous system
- MeSH terms
- Adrenal Medulla, Adrenergic beta-Antagonists, Animals, Behavior, Animal, Bradykinin, Dose-Response Relationship, Drug, Drug Interactions, Epinephrine, Hyperalgesia, Male, Pain Measurement, Physical Stimulation, Propanolamines, Propranolol, Time Factors, Vagotomy, Vagus Nerve, Rats, Sprague-Dawley, Pain Threshold, Rats
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