Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain
Open accessAbstract
Selective activation of the peripheral cannabinoid receptor 1 (CB1R) has been shown to suppress neuropathic pain symptoms in rodents. However, relatively little is known about changes in CB1R and its endogenous ligands during development or maintenance of neuropathic pain. Using immunohistochemistry, Western blot, real-time reverse transcription polymerase chain reaction, as well as liquid chromatography/mass spectrometry, we studied the changes in CB1Rs and endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in rat lumbar (L4 and L5) dorsal root ganglia (DRG) after neuropathic pain induction (L5 spinal nerve ligation: SNL). Immunohistochemistry revealed that in control rats, CB1R is expressed in the majority (76-83%) of nociceptive neurons as indicated by co-labeling with isolectin B4 (IB4) or antibodies recognizing transient receptor potential vanilloid (TRPV1), calcitonin gene related peptide (CGRP), and the NR2C/2D subunits of the N-methyl-D-aspartate receptor. After L5 SNL, CB1R mRNA and protein increases in the ipsilateral uninjured L4 DRG whereas the percentages of CB1R immunoreactive (CB1R-ir) neurons remain unchanged in L4 and L5 DRG. However, for these CB1R-ir neurons, we observe significant increases in percentage of TRPV1-ir cells in ipsilateral L4 DRG, and decreases in percentage of IB4- and CGRP-co-labeled cells in ipsilateral L5 DRG. Levels of both AEA and 2-AG increase significantly only in the ipsilateral L5 DRG. These results are consistent with the preserved analgesic effects of cannabinoids in neuropathic pain and provide a rational framework for the development of peripherally acting endocannabinoid-based therapeutic interventions for neuropathic pain.
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Increases in CB1 mRNA are observed in the uninjured L4 dorsal root ganglion ipsilateral to injury after SNL.
“Increases in CB1 mRNA are observed in the uninjured (but abnormal) L4 DRG ipsilateral to injury.83”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [83]
Increases in both AEA and 2-AG have been reported in the ipsilateral injured L5, but not the uninjured L4 dorsal root ganglion after SNL.
“Increases in both AEA and 2-AG have also been reported in the ipsilateral injured L5, but not the uninjured L4 DRG.83”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [83]
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- Authors
- Mitrirattanakul, S., Ramakul, N., Guerrero, A. V., Matsuka, Y., Ono, T., Iwase, H., Mackie, K., Faull, K. F., & Spigelman, I.
- Affiliations
- University of California, Los Angeles (US)
- University of Washington (US)
- Corresponding author
- Spigelman, Igor
- Venue
- Pain
- Published
- 2006-12
- Volume
- 126
- Issue
- 1
- Pages
- 102-114
- ISSN
- 0304-3959 (ISSN-L)
- PMC
- PMC1776167
- OpenAlex
- W2078921285
- Cited by
- 207
- References
- 90
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 5 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 7 · 2018: 14 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 11 · 2013: 9 · 2012: 18
- FWCI
- 10.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (DA00286, DA11322, R01DA011322, K02DA000286)
- National Institute of Dental and Craniofacial Research (DE14573, K08DE014573)
- 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
- CB1R, neuropathic pain, endocannabinoids, anandamide, 2-arachidonoylglycerol, dorsal root ganglia, spinal nerve ligation, TRPV1, calcitonin gene-related peptide, nociceptors
- MeSH terms
- Animals, Ganglia, Spinal, Hot Temperature, Immunohistochemistry, Ligands, Ligation, Lumbosacral Region, Male, Neuralgia, Physical Stimulation, RNA, Messenger, Spinal Nerves, Tissue Distribution, Rats, Sprague-Dawley, Receptors, Cannabinoid, Receptor, Cannabinoid, CB1, Rats, Cannabinoid Receptor Modulators
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