Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins genotype-dependent hyper-responsivity to noxious stimuli

Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins hyper-responsivity to a noxious inflammatory stimulus in the Wistar–Kyoto rat, a genetic background prone to heightened stress/affect. Pain is both a sensory and an emotional experience, and is subject to modulation by...

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Published inPain (Amsterdam) Vol. 155; no. 1; pp. 69 - 79
Main Authors Rea, Kieran, Olango, Weredeselam M., Okine, Bright N., Madasu, Manish K., McGuire, Iseult C., Coyle, Kathleen, Harhen, Brendan, Roche, Michelle, Finn, David P.
Format Journal Article
LanguageEnglish
Published Philadelphia, PA Elsevier B.V 01.01.2014
International Association for the Study of Pain
Elsevier
Subjects
Affect
Anandamide
Animals
Biological and medical sciences
Cannabinoid Receptor Modulators - pharmacology
Cannabinoid1 (CB1) receptor
Depression - psychology
Disease Models, Animal
Endocannabinoids - genetics
Endocannabinoids - metabolism
Fatty acid amide hydrolase (FAAH)
Formaldehyde - toxicity
Formalin
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Hyperkinesis - psychology
Male
Medical sciences
Medulla Oblongata - drug effects
Medulla Oblongata - metabolism
Microdissection
Neuropharmacology
Nociception - drug effects
Nociception - physiology
Pain
Pain Measurement
Pharmacology. Drug treatments
Psychodysleptics: hallucinogen
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Random Allocation
Rats
Rats, Inbred WKY
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 - metabolism
Rostroventromedial medulla (RVM)
Signal Transduction - drug effects
Signal Transduction - physiology
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors
Vertebrates: nervous system and sense organs
Wistar–Kyoto rat
Pain
Fatty acid amide hydrolase (FAAH)
Rostroventromedial medulla (RVM)
Formalin
Cannabinoid1 (CB1) receptor
Affect
Wistar–Kyoto rat
Anandamide
CB1 cannabinoid receptor
Noxious stimulus
Rat
Lipids
Cannabinoid
Genetic determinism
Endocannabinoid
Wistar-Kyoto rat
Genetics
CB
Enzyme
Rodentia
Genotype
Fatty acids
Vertebrata
Mammalia
receptor
Animal
Hydrolases
Cannabinoid (CB) receptor
Online AccessGet full text
ISSN0304-3959
1872-6623
1872-6623
DOI10.1016/j.pain.2013.09.012

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Abstract Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins hyper-responsivity to a noxious inflammatory stimulus in the Wistar–Kyoto rat, a genetic background prone to heightened stress/affect. Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar–Kyoto (WKY) rat exhibits a stress-hyper-responsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid1 (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical, and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.
AbstractList Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins hyper-responsivity to a noxious inflammatory stimulus in the Wistar–Kyoto rat, a genetic background prone to heightened stress/affect. Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar–Kyoto (WKY) rat exhibits a stress-hyper-responsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid1 (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical, and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.
Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar-Kyoto (WKY) rat exhibits a stress-hyper-responsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid1 (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical, and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar-Kyoto (WKY) rat exhibits a stress-hyper-responsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid1 (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical, and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.
Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect. The Wistar-Kyoto (WKY) rat exhibits a stress-hyper-responsive and depressive-like phenotype and increased sensitivity to noxious stimuli, compared with other rat strains. Here, we show that this genotype-dependent hyperalgesia is associated with impaired pain-related mobilisation of endocannabinoids and transcription of their synthesising enzymes in the rostral ventromedial medulla (RVM). Pharmacological blockade of the Cannabinoid1 (CB1) receptor potentiates the hyperalgesia in WKY rats, whereas inhibition of the endocannabinoid catabolising enzyme, fatty acid amide hydrolase, attenuates the hyperalgesia. The latter effect is mediated by CB1 receptors in the RVM. Together, these behavioural, neurochemical, and molecular data indicate that impaired endocannabinoid signalling in the RVM underpins hyper-responsivity to noxious stimuli in a genetic background prone to heightened stress/affect.
Author Madasu, Manish K.
Okine, Bright N.
Olango, Weredeselam M.
Finn, David P.
Coyle, Kathleen
Harhen, Brendan
Roche, Michelle
Rea, Kieran
McGuire, Iseult C.
AuthorAffiliation Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland Physiology, School of Medicine, National University of Ireland, Galway, Ireland NCBES Galway Neuroscience Centre and Centre for Pain Research, National University of Ireland, Galway, Ireland
AuthorAffiliation_xml – name: Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland Physiology, School of Medicine, National University of Ireland, Galway, Ireland NCBES Galway Neuroscience Centre and Centre for Pain Research, National University of Ireland, Galway, Ireland
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  organization: Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland
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Issue 1
Keywords Pain
Fatty acid amide hydrolase (FAAH)
Rostroventromedial medulla (RVM)
Formalin
Cannabinoid1 (CB1) receptor
Affect
Wistar–Kyoto rat
Anandamide
CB1 cannabinoid receptor
Noxious stimulus
Rat
Lipids
Cannabinoid
Genetic determinism
Endocannabinoid
Wistar-Kyoto rat
Genetics
CB
Enzyme
Rodentia
Genotype
Fatty acids
Vertebrata
Mammalia
receptor
Animal
Hydrolases
Cannabinoid (CB) receptor
Language English
License CC BY 4.0
Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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PublicationTitle Pain (Amsterdam)
PublicationTitleAlternate Pain
PublicationYear 2014
Publisher Elsevier B.V
International Association for the Study of Pain
Elsevier
Publisher_xml – name: Elsevier B.V
– name: International Association for the Study of Pain
– name: Elsevier
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Snippet Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins hyper-responsivity to a noxious inflammatory stimulus in the Wistar–Kyoto...
Pain is both a sensory and an emotional experience, and is subject to modulation by a number of factors including genetic background modulating stress/affect....
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StartPage 69
SubjectTerms Affect
Anandamide
Animals
Biological and medical sciences
Cannabinoid Receptor Modulators - pharmacology
Cannabinoid1 (CB1) receptor
Depression - psychology
Disease Models, Animal
Endocannabinoids - genetics
Endocannabinoids - metabolism
Fatty acid amide hydrolase (FAAH)
Formaldehyde - toxicity
Formalin
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
Hyperkinesis - psychology
Male
Medical sciences
Medulla Oblongata - drug effects
Medulla Oblongata - metabolism
Microdissection
Neuropharmacology
Nociception - drug effects
Nociception - physiology
Pain
Pain Measurement
Pharmacology. Drug treatments
Psychodysleptics: hallucinogen
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Random Allocation
Rats
Rats, Inbred WKY
Rats, Sprague-Dawley
Receptor, Cannabinoid, CB1 - metabolism
Rostroventromedial medulla (RVM)
Signal Transduction - drug effects
Signal Transduction - physiology
Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors
Vertebrates: nervous system and sense organs
Wistar–Kyoto rat
Title Impaired endocannabinoid signalling in the rostral ventromedial medulla underpins genotype-dependent hyper-responsivity to noxious stimuli
URI https://dx.doi.org/10.1016/j.pain.2013.09.012
https://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00006396-201401000-00014
https://www.ncbi.nlm.nih.gov/pubmed/24076311
https://www.proquest.com/docview/1490706670
Volume 155
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