Charlie H-T. Kwok
Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development
H-T. Kwok, Charlie; Devonshire, Ian M.; Imraish, Amer; Greenspon, Charles M.; Lockwood, Stevie; Fielden, Catherine; Cooper, Andrew; Woodhams, Stephen; Sarmad, Sarir; Ortori, Catherine A.; Barrett, David A.; Kendall, David; Bennett, Andrew J.; Chapman, Victoria; Hathway, Gareth J.
Authors
Ian M. Devonshire
Amer Imraish
Charles M. Greenspon
Stevie Lockwood
Catherine Fielden
Andrew Cooper
Dr STEPHEN WOODHAMS STEPHEN.WOODHAMS@NOTTINGHAM.AC.UK
Research Fellow
Dr SARIR SARMAD Sarir.Sarmad@nottingham.ac.uk
SENIOR TEACHING TECHNICIAN
Catherine A. Ortori
David A. Barrett
David Kendall
Dr ANDREW BENNETT ANDREW.BENNETT@NOTTINGHAM.AC.UK
ASSOCIATE PROFESSOR
Professor VICTORIA CHAPMAN VICTORIA.CHAPMAN@NOTTINGHAM.AC.UK
PROFESSOR OF NEUROPHARMACOLOGY
Professor GARETH HATHWAY gareth.hathway@nottingham.ac.uk
PROFESSOR OF NEUROSCIENCE
Abstract
Significant age and experience-dependent remodelling of spinal and supraspinal neural networks occur resulting in altered pain responses in early life. In adults endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here we have studied the changing role of the ECs in brainstem nuclei essential for the control of nociception from birth to adulthood in both rat and human. Using in vivo electrophysiology we show that substantial functional changes occur in the effect of microinjection of ECs receptor agonists and antagonists in the periaqueductal grey (PAG) and rostroventral medulla (RVM), both of which play central roles in the supraspinal control of pain and the maintenance of chronic pain states in adulthood. We show that in immature PAG and RVM the orphan receptor GPR55 is able to mediate profound analgesia which is absent in adults. We show that tissue levels of endocannabinoid neurotransmitters, anandamide and 2-arachidonoylglycerol within the PAG and RVM are developmentally regulated (using mass spectrometry). The expression patterns and levels of ECs enzymes and receptors were assessed using quantitative PCR and immunohistochemistry. In human brainstem we show age-related alterations in the expression of key enzymes and receptors in involved in ECs function using PCR and in situ hybridisation. These data reveal significant changes on ECs that to this point have been unknown and which shed new light into the complex neurochemical changes that permit normal, mature responses to pain.
Citation
H-T. Kwok, C., Devonshire, I. M., Imraish, A., Greenspon, C. M., Lockwood, S., Fielden, C., Cooper, A., Woodhams, S., Sarmad, S., Ortori, C. A., Barrett, D. A., Kendall, D., Bennett, A. J., Chapman, V., & Hathway, G. J. (2017). Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development. PAIN, 158(11), 2222-2232. https://doi.org/10.1097/j.pain.0000000000001027
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 20, 2017 |
Online Publication Date | Nov 1, 2017 |
Publication Date | Nov 1, 2017 |
Deposit Date | Aug 21, 2017 |
Publicly Available Date | Nov 1, 2017 |
Journal | PAIN |
Print ISSN | 0304-3959 |
Electronic ISSN | 1872-6623 |
Publisher | Lippincott, Williams & Wilkins |
Peer Reviewed | Peer Reviewed |
Volume | 158 |
Issue | 11 |
Pages | 2222-2232 |
DOI | https://doi.org/10.1097/j.pain.0000000000001027 |
Keywords | pain; RVM; PAG; development; postnatal; endocannabinoid;descending control; |
Public URL | https://nottingham-repository.worktribe.com/output/891906 |
Publisher URL | https://insights.ovid.com/crossref?an=00006396-201711000-00020 |
Contract Date | Aug 21, 2017 |
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Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
Kwok et al Pain 2017 (accepted).pdf
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0
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