Involvement of the opioid and cannabinoid systems in pain control: New insights from knockout studies
Abstract
The endogenous opioid and cannabinoid systems are involved in the physiological inhibitory control of pain and are of particular interest for the development of therapeutic approaches for pain management. The involvement of these endogenous systems in pain control has been studied from decades by the use of compounds with different affinities for each cannabinoid and opioid receptor or for the different enzymes involved in endocannabinoid and endogenous opioid metabolism. However, the selectivity of these pharmacological tools in vivo has represented an important limitation for these studies. The generation of genetically modified mice with selective mutations in specific components of the endocannabinoid and endogenous opioid system has provided important advances in the identification of the specific contribution of each component of these endogenous systems in the perception of noxious stimuli and the development of pathological pain states. Different lines of constitutive and conditional knockout mice deficient in specific cannabinoid and opioid receptors, specific precursors of the endogenous opioid peptides and the main enzymes involved in endocannabinoid and endogenous opioid degradation are now available. These knockout mice have also been used to evaluate the contribution of each component of the endocannabinoid and opioid system in the antinociceptive effects of cannabinoid and opioid agonists, including those currently used to treat pain in humans. This review summarizes the main advances provided in the last 15 years by the use of these genetic tools in the knowledge of the physiological control of pain and the pharmacology of cannabinoid and opioid compounds for pain management.
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CB1-/- mice show a pain-induced increase in time spent in the dark area of the light/dark test and decreased time and travel distance in the open area of the zero-maze apparatus.
“but rather a pain-induced increase in time spent in the dark area of the light/dark test, and decreased time and travel distance in the open area of the zero-maze apparatus.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Nadal et al, 2013
CB1-/- mice do not display apparent altered nociception.
“However, it is noteworthy that CB 1 ( -/ -) mice do not display apparent altered nociception (Nadal et al, 2013), but rather a pain-induced increase in time spent in the dark area of the light/dark test, and decreased time and travel distance in the open area of the zero-maze apparatus.”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Nadal et al, 2013
The development and expression of neuropathic pain were not modified in FAAH or MAGL-/- mice.
“On the other hand, the development and expression of neuropathic pain were not modified in FAAH or MAGL ( -/ -) mice (Nadal et al, 2013;Schlosburg et al, 2010).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Nadal et al, 2013
CB1 and CB2 receptor agonists produce antinociceptive effects in laboratory animal models of neuropathic pain.
“CB 1 and CB 2 receptor agonists produce antinociceptive effects in laboratory animal models of neuropathic pain (Nadal et al, 2013).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Nadal et al, 2013
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- Authors
- Nadal, X., La Porta, C., Andreea Bura, S., & Maldonado, R.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Maldonado, Rafael
- ORCID
- Maldonado, Rafael
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 716
- Issue
- 1-3
- Pages
- 142-157
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2094638520
- Cited by
- 76
- References
- 161
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 6 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 9 · 2016: 8 · 2015: 7 · 2014: 6 · 2013: 1
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- endogenous opioid system, endocannabinoid system, pain management, knockout mice, cannabinoid receptors, opioid receptors, endogenous opioids, antinociception, pathological pain, cannabinoid receptor agonists, opioid agonists
- MeSH terms
- Analgesics, Opioid, Animals, Cannabinoids, Pain, Gene Knockout Techniques
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