Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity

Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal roo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zachary K. Ford, Ashlie N. Reker, Sisi Chen, Feni Kadakia, Alexander Bunk, Steve Davidson
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	pain cannabinoid dorsal root ganglia inflammation TRPV1 sensory neuron Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3ac35d44880a441bbd55fbb7a9d55a1a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3ac35d44880a441bbd55fbb7a9d55a1a
record_format	dspace
spelling	oai:doaj.org-article:3ac35d44880a441bbd55fbb7a9d55a1a2021-11-16T05:49:57ZCannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity2673-561X10.3389/fpain.2021.721332https://doaj.org/article/3ac35d44880a441bbd55fbb7a9d55a1a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fpain.2021.721332/fullhttps://doaj.org/toc/2673-561XCannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood–brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.Zachary K. FordAshlie N. RekerSisi ChenFeni KadakiaAlexander BunkSteve DavidsonSteve DavidsonFrontiers Media S.A.articlepaincannabinoiddorsal root gangliainflammationTRPV1sensory neuronNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Pain Research, Vol 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pain cannabinoid dorsal root ganglia inflammation TRPV1 sensory neuron Neurology. Diseases of the nervous system RC346-429
spellingShingle	pain cannabinoid dorsal root ganglia inflammation TRPV1 sensory neuron Neurology. Diseases of the nervous system RC346-429 Zachary K. Ford Ashlie N. Reker Sisi Chen Feni Kadakia Alexander Bunk Steve Davidson Steve Davidson Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
description	Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood–brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.
format	article
author	Zachary K. Ford Ashlie N. Reker Sisi Chen Feni Kadakia Alexander Bunk Steve Davidson Steve Davidson
author_facet	Zachary K. Ford Ashlie N. Reker Sisi Chen Feni Kadakia Alexander Bunk Steve Davidson Steve Davidson
author_sort	Zachary K. Ford
title	Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
title_short	Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
title_full	Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
title_fullStr	Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
title_full_unstemmed	Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity
title_sort	cannabinoid receptor 1 expression in human dorsal root ganglia and cb13-induced bidirectional modulation of sensory neuron activity
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3ac35d44880a441bbd55fbb7a9d55a1a
work_keys_str_mv	AT zacharykford cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT ashlienreker cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT sisichen cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT fenikadakia cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT alexanderbunk cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT stevedavidson cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity AT stevedavidson cannabinoidreceptor1expressioninhumandorsalrootgangliaandcb13inducedbidirectionalmodulationofsensoryneuronactivity
_version_	1718426660913545216

Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity

Ejemplares similares