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The Role of the Endocannabinoid System in Pain

  • Chapter
Pain Control

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 227))

Abstract

Preparations of the Cannabis sativa plant have been used to analgesic effect for millenia, but only in recent decades has the endogenous system responsible for these effects been described. The endocannabinoid (EC) system is now known to be one of the key endogenous systems regulating pain sensation, with modulatory actions at all stages of pain processing pathways. The EC system is composed of two main cannabinoid receptors (CB1 and CB2) and two main classes of endogenous ligands or endocannabinoids (ECs). The receptors have distinct expression profiles, with CB1 receptors found at presynaptic sites throughout the peripheral and central nervous systems (PNS and CNS, respectively), whilst CB2 receptor is found principally (but not exclusively) on immune cells. The endocannabinoid ligands are lipid neurotransmitters belonging to either the N-acyl ethanolamine (NAEs) class, e.g. anandamide (AEA), or the monoacylglycerol class, e.g. 2-arachidonoyl glycerol (2-AG). Both classes are short-acting transmitter substances, being synthesised on demand and with signalling rapidly terminated by specific enzymes. ECs acting at CB1 negatively regulate neurotransmission throughout the nervous system, whilst those acting at CB2 regulate the activity of CNS immune cells. Signalling through both of these receptor subtypes has a role in normal nociceptive processing and also in the development resolution of acute pain states. In this chapter, we describe the general features of the EC system as related to pain and nociception and discuss the wealth of preclinical and clinical data involving targeting the EC system with focus on two areas of particular promise: modulation of 2-AG signalling via specific enzyme inhibitors and the role of spinal CB2 in chronic pain states.

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Abbreviations

2-AG:

2-Arachidonoyl glycerol

Δ9-THC:

Δ9-Tetrahydrocannabinol

ABHD6:

αβ-Hydrolase domain 6

ABHD12:

αβ-Hydrolase domain 12

ACC:

Anterior cingulate cortex

AEA:

Anandamide

AM251:

A CB1 selective receptor inverse agonist/antagonist

CB1 :

Cannabinoid type 1 receptor

CB2 :

Cannabinoid type 2 receptor

CCI:

Chronic constriction injury (neuropathic pain model)

CNS:

Central nervous system

DAGLα:

Diacylglycerol lipase-α

DRG:

Dorsal root ganglia

EC:

Endocannabinoid

FAAH:

Fatty acid amide hydrolase

fMRI:

Functional magnetic resonance imaging

GPCR:

G protein-coupled receptor

MAG:

Monoacylglycerol

MAGL:

Monoacylglycerol lipase

NAE:

N-acylethanolamine

NAPE-PLD:

N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D

PAG:

Periaqueductal grey matter

PKC:

Protein kinase C

PNS:

Peripheral nervous system

RVM:

Rostral ventromedial medulla

SR144528:

A CB2 selective receptor antagonist

TRPV1:

Transient receptor potential vanilloid 1

WDR:

Wide dynamic range neuron; a class of spinal neuron with key involvement in the transduction of nociceptive input

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Acknowledgements

D.S. and J.J.B. are funded by Arthritis Research UK Pain Centre funding (grant no. 18769).

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Authors and Affiliations

  1. Momentum Laboratory of Molecular Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, 1083, Hungary

    Stephen G. Woodhams

  2. Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, NG7 2UH, UK

    Devi Rani Sagar, James J. Burston & Victoria Chapman

  3. School of Life Sciences, Queen’s Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK

    Devi Rani Sagar, James J. Burston & Victoria Chapman

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  1. Stephen G. Woodhams
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  2. Devi Rani Sagar
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  4. Victoria Chapman
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Correspondence to Victoria Chapman .

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  1. Institute of Physiology/Neurophysiology, Jena University Hospital, Jena, Thüringen, Germany

    Hans-Georg Schaible

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Woodhams, S.G., Sagar, D.R., Burston, J.J., Chapman, V. (2015). The Role of the Endocannabinoid System in Pain. In: Schaible, HG. (eds) Pain Control. Handbook of Experimental Pharmacology, vol 227. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-46450-2_7

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