The Endocannabinoid System and Pain

Guindon, Josee; Hohmann, Andrea

doi:10.2174/187152709789824660

Cited by 476Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsIon Channels and Receptors

The Endocannabinoid System and Pain

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Guindon, Josee, Hohmann, Andrea·2009·CNS & Neurological Disorders - Drug Targets

DOI 10.2174/187152709789824660PMC PMC2834283

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Abstract

The therapeutic potential of cannabinoids has been the topic of extensive investigation following the discovery of cannabinoid receptors and their endogenous ligands. Cannabinoid receptors and their endogenous ligands are present at supraspinal, spinal and peripheral levels. Cannabinoids suppress behavioral responses to noxious stimulation and suppress nociceptive processing through activation of cannabinoid CB(1) and CB(2) receptor subtypes. Endocannabinoids, the brain's own cannabis-like substances, share the same molecular target as Delta(9)-tetrahydrocannabinol, the main psychoactive component in cannabis. Endocannabinoids serve as synaptic circuit breakers and regulate multiple physiological and pathological conditions, e.g. regulation of food intake, immunomodulation, inflammation, analgesia, cancer, addictive behavior, epilepsy and others. This review will focus on uncovering the roles of anandamide and 2-arachidonoylglycerol, the two best characterized endocannabinoids identified to date, in controlling nociceptive responding. The roles of anandamide and 2-arachidonoylglycerol, released under physiological conditions, in modulating nociceptive responding at different levels of the neuraxis will be emphasized in this review. Effects of modulation of endocannabinoid levels through inhibition of endocannabinoid hydrolysis and uptake is also compared with effects of exogenous administration of synthetic endocannabinoids in acute, inflammatory and neuropathic pain models. Finally, the therapeutic potential of the endocannabinoid signaling system is discussed in the context of identifying novel pharmacotherapies for the treatment of pain.

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Cannabinoid-induced antinociception is reported in a variety of preclinical inflammatory pain models, including intraplantar injection of carrageenan and LPS.
“Cannabinoidinduced antinociception is reported in a variety of preclinical inflammatory pain models (Table 2; also see a review by Guindon and Hohmann, 2009), including intraplantar injection (that is, into the ventral footpad) of the seaweed extract carrageenan, and the Gram-negative bacterial-derived endotoxin lipopolysaccharide (LPS).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Guindon and Hohmann, 2009
Using complementary genetic and pharmacological approaches, distinct components of the endocannabinoid system (receptors and endocannabinoid-regulating enzymes) have emerged as promising targets to treat neuropathic pain.
“Using complementary genetic and pharmacological approaches, distinct components of the endocannabinoid system (ie, receptors and endocannabinoid-regulating enzymes) have emerged as promising targets to treat neuropathic pain (Table 5; for additional information, Guindon and Hohmann, 2009;Rahn and Hohmann, 2009).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Guindon and Hohmann, 2009
The finding supports previous work demonstrating the potential of the endocannabinoid system as a target for new therapies to alleviate pain.
“and supports a growing body of previous work in numerous contexts demonstrating the considerable potential of the endocannabinoid system as a target for the development of new therapies to alleviate pain [14,17].”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [17]
Little is known about mechanisms by which the endocannabinoid system and exogenous cannabinoid agents act to influence pain in the specific context of endometriosis-associated pain.
“Although mechanisms by which the endocannabinoid system and exogenous cannabinoid agents act to influence pain are under intense study [14,17], little is known in the specific context of endometriosis-associated pain.”
From Endocannabinoid involvement in endometriosis. (2010) · cites this paper as [17]

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“In the formalin test, endocannabinoid uptake inhibitors (AM404, UCM707, LY2318912, LY2183240, OMDM132) produce antinociception [93,214,215] (see Table 3).”
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“The finding here that a cannabinoid agent alleviates hyperalgesia in a rat model of endometriosis is consistent with the known efficacy of cannabinoid agents in women with endometriosis [45] and supports a growing body of previous work in numerous contexts demonstrating the considerable potential of the endocannabinoi…”
BackgroundResult

Authors: Guindon, J., & Hohmann, A.
Affiliations: University of Georgia (US)
Corresponding author: Hohmann, Andrea
ORCID: Hohmann, Andrea
Venue: CNS & Neurological Disorders - Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2009-12-01
Volume: 8
Issue: 6
Pages: 403-421
ISSN: 1568-007X (ISSN-L)
1871-5273
DOI: 10.2174/187152709789824660
PMC: PMC2834283
OpenAlex: W2054998310
Cited by: 476
References: 255
Citations by year: 2026: 21 · 2025: 19 · 2024: 36 · 2023: 27 · 2022: 41 · 2021: 38 · 2020: 23 · 2019: 25 · 2018: 33 · 2017: 27 · 2016: 23 · 2015: 23 · 2014: 39 · 2013: 28 · 2012: 36
FWCI: 17.25
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: CNS & Neurological Disorders - Drug Targets (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Drug Abuse (DA022478, DA-022702, R21DA022478, R01DA021644, R21DA022702, DA021644)
Topics: Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
Keywords: endocannabinoid system, pain, anandamide, 2-arachidonoylglycerol, cannabinoid receptors, CB1 receptor, CB2 receptor, nociception, analgesia, neuropathic pain, inflammatory pain, synthetic cannabinoids, pharmacological pain management
MeSH terms: Animals, Arachidonic Acids, Brain, Glycerides, Humans, Pain, Receptors, Cannabinoid, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids

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The Endocannabinoid System and Pain

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