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Central and peripheral sites of action for CB 2 receptor mediated analgesic activity in chronic inflammatory and neuropathic pain models in rats
Open accessAbstract
BACKGROUND AND PURPOSE Cannabinoid CB 2 receptor activation by selective agonists has been shown to produce analgesic effects in preclinical models of inflammatory and neuropathic pain. However, mechanisms underlying CB 2 ‐mediated analgesic effects remain largely unknown. The present study was conducted to elucidate the CB 2 receptor expression in ‘pain relevant’ tissues and the potential sites of action of CB 2 agonism in rats. EXPERIMENTAL APPROACH Expression of cannabinoid receptor mRNA was evaluated by quantitative RT‐PCR in dorsal root ganglia (DRGs), spinal cords, paws and several brain regions of sham, chronic inflammatory pain (CFA) and neuropathic pain (spinal nerve ligation, SNL) rats. The sites of CB 2 mediated antinociception were evaluated in vivo following intra‐DRG, intrathecal (i.t.) or intraplantar (i.paw) administration of potent CB 2 ‐selective agonists A‐836339 and AM1241. KEY RESULTS CB 2 receptor gene expression was significantly up‐regulated in DRGs (SNL and CFA), spinal cords (SNL) or paws (CFA) ipsilateral to injury under inflammatory and neuropathic pain conditions. Systemic A‐836339 and AM1241 produced dose‐dependent efficacy in both inflammatory and neuropathic pain models. Local administration of CB 2 agonists also produced significant analgesic effects in SNL (intra‐DRG and i.t.) and CFA (intra‐DRG) pain models. In contrast to A‐836339, i.paw administration of AM‐1241 dose‐relatedly reversed the CFA‐induced thermal hyperalgesia, suggesting that different mechanisms may be contributing to its in vivo properties. CONCLUSIONS AND IMPLICATIONS These results demonstrate that both DRG and spinal cord are important sites contributing to CB 2 receptor‐mediated analgesia and that the changes in CB 2 receptor expression play a crucial role for the sites of action in regulating pain perception.
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“CFA administration into a ventral footpad leads to upregulation of CB 2 receptors, but not CB 2 receptor mRNA in dorsal root ganglia or ipsilateral paw tissue of rats, suggesting that these receptors play an integral role in the endocannabinoid modulation of chronic inflammatory pain (Hsieh et al, 2011).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Hsieh et al, 2011
In the citing paper
“Acute administration of CB 2 receptor agonists reduces CFA-induced mechanical and thermal hyperalgesia (Hsieh et al, 2011;Valenzano et al, 2005;Yao et al, 2008Yao et al, , 2009)).”
From The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain (2018) · cites this paper as Hsieh et al, 2011
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Metadata
- Authors
- Hsieh, G. C., Pai, M., Chandran, P., Hooker, B. A., Zhu, C. Z., Salyers, A. K., Wensink, E. J., Zhan, C., Carroll, W. A., Dart, M. J., Yao, B. B., Honore, P., & Meyer, M. D.
- Affiliations
- Abbott (United States) (US)
- Corresponding author
- Hsieh, Gin C
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2010-12-14
- Volume
- 162
- Issue
- 2
- Pages
- 428-440
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3031063
- OpenAlex
- W1594786713
- Cited by
- 139
- References
- 58
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 7 · 2014: 12 · 2013: 19 · 2012: 9
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- CB2 receptor, cannabinoid analgesia, neuropathic pain, inflammatory pain, dorsal root ganglia, spinal cord, AM1241, intrathecal administration, receptor gene expression, thermal hyperalgesia, spinal nerve ligation, complete Freund's adjuvant
- MeSH terms
- Analgesia, Analgesics, Animals, Brain, Cannabinoids, Disease Models, Animal, Ganglia, Spinal, Inflammation, Male, Neuralgia, Pain, RNA, Messenger, Spinal Cord, Thiazoles, Rats, Sprague-Dawley, Opioid Peptides, Receptor, Cannabinoid, CB2, Rats, Pain Perception
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