Cited by 208Cannabis and Cannabinoid ResearchPain Mechanisms and TreatmentsIon Channels and Receptors

Site-specific increases in peripheral cannabinoid receptors and their endogenous ligands in a model of neuropathic pain

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Mitrirattanakul, Somsak, Ramakul, Navapoln, Guerrero, Andre V., Matsuka, Yoshizo, Ono, Takeshi, Iwase, Hirotate, Mackie, Ken, Faull, Kym F. +1 more·2006·Pain

Abstract

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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Crossref · 10.1016/j.pain.2006.06.016

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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)
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
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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