Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development

Kwok, C. H.-T. et al. (2017) Age-dependent plasticity in endocannabinoid modulation of pain processing through postnatal development. Pain, 158(11), pp. 2222-2232. (doi: 10.1097/j.pain.0000000000001027) (PMID:28767505) (PMCID:PMC5642337)

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 the brainstem nuclei essential for the control of nociception from birth to adulthood in both rats and humans. 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 involved in ECs function using PCR and in situ hybridisation. These data reveal that 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

• Item Type: Articles
• Additional Information: This work was supported by the Biotechnology and Biological Sciences Research Council [grant number BB/I001565/1], and by a BBSRC PhD studentship.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cooper, Dr Andrew
• Authors: Kwok, C. H.-T., Devonshire, I. M., Imraish, A., Greenspon, C., Lockwood, S., Fielden, C., Cooper, A., Woodhams, S., Sarmad, S., Ortori, C. A., Barrett, D. A., Kendall, D., Bennett, A. J., Chapman, V., and Hathway, G. J.
• Subjects: Q Science > QP Physiology
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Pain
• Publisher: Lippincott, Williams & Wilkins
• ISSN: 0304-3959
• ISSN (Online): 1872-6623
• Published Online: 01 August 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Pain 158(11): 2222-2232
• Publisher Policy: Reproduced under a Creative Commons License