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

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.

• Authors: Charlie H-T Kwok, Ian M Devonshire, Amer Imraish, Charles M Greenspon, Stevie Lockwood, Catherine Fielden, Andrew Cooper, Stephen Woodhams, Sarir Sarmad, Catherine A Ortori, David A Barrett, David Kendall, Andrew J Bennett, Victoria Chapman, Gareth J Hathway
• Journal: Pain (Pain) Vol. 158 Issue 11 Pg. 2222-2232 (Nov 2017) ISSN: 1872-6623 [Electronic] United States
• PMID: 28767505 (Publication Type: Journal Article)

Chemical References

• Arachidonic Acids
• Endocannabinoids
• GPR55 protein, rat
• Opioid Peptides
• Polyunsaturated Alkamides
• RNA, Messenger
• Receptors, Cannabinoid
• Receptors, G-Protein-Coupled
• Napepld protein, rat
• Phospholipase D
• anandamide

Topics

• Age Factors
• Aging (physiology)
• Animals
• Animals, Newborn
• Arachidonic Acids (therapeutic use)
• Disease Models, Animal
• Endocannabinoids (genetics, metabolism, therapeutic use)
• Gene Expression Regulation, Developmental (drug effects, physiology)
• Medulla Oblongata (drug effects, growth & development)
• Microinjections
• Neuronal Plasticity (physiology)
• Opioid Peptides (metabolism, pharmacology)
• Pain (drug therapy, metabolism)
• Pain Measurement
• Periaqueductal Gray (drug effects, growth & development)
• Phospholipase D (genetics, metabolism)
• Polyunsaturated Alkamides (therapeutic use)
• RNA, Messenger (metabolism)
• Rats
• Receptors, Cannabinoid (genetics, metabolism)
• Receptors, G-Protein-Coupled (genetics, metabolism)