The DOI matches its Crossref record; 56 of the 58 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Ethical guidelines for investigations of experimental pain in conscious animals.
Zimmermann, M. (1983) · Pain · doi:10.1016/0304-3959(83)90201-4 · Cited by 7,762
Quantitative assessment of tactile allodynia in the rat paw
Chaplan, S. R., Bach, F. W., Pogrel, J. W., Chung, J. M., & Yaksh, T. L. (1994) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(94)90144-9 · Cited by 7,740
A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man
Bennett, G. J., & Xie, Y.-K. (1988) · Pain · doi:10.1016/0304-3959(88)90209-6 · Cited by 5,376
A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia
Hargreaves, K., Dubner, R. A., Brown, F. J., Flores, C., & Joris, J. L. (1988) · Pain · doi:10.1016/0304-3959(88)90026-7 · Cited by 5,155
Molecular characterization of a peripheral receptor for cannabinoids
Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993) · Nature · doi:10.1038/365061a0 · Cited by 5,092
Structure of a cannabinoid receptor and functional expression of the cloned cDNA
Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990) · Nature · doi:10.1038/346561a0 · Cited by 5,011
Ho Kim, S., & Mo Chung, J. (1992) · Pain · doi:10.1016/0304-3959(92)90041-9 · Cited by 3,069
Efficient Analysis of Experimental Observations
Dixon, W. J. (1980) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.20.040180.002301 · Cited by 2,216
Chronic catheterization of the spinal subarachnoid space
Yaksh, T. L., & Rudy, T. A. (1976) · Physiology & Behavior · doi:10.1016/0031-9384(76)90029-9 · Cited by 2,197
Guide to receptors and channels (GRAC), 5th edition
Alexander, S., Mathie, A., & Peters, J. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01649_1.x · Cited by 1,947
Galiègue, S., Mary, S., Marchand, J., Dussossoy, D., Carrière, D., Carayon, P., Bouaboula, M., Shire, D. J., Fur, G. L., & Casellas, P. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20780.x · Cited by 1,776
Pharmacology of cannabinoid CB1 and CB2 receptors
Pertwee, R. G. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(97)82001-3 · Cited by 1,526
Bisogno, T., Hanuš, L., PETROCELLIS, L. D., Tchilibon, S., Ponde, D. E., Brandi, I., Moriello, A. S., Davis, J. B., Mechoulam, R., & Marzo, V. D. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704327 · Cited by 1,315
Glial activation: a driving force for pathological pain
Watkins, L. R., Milligan, E. D., & Maier, S. F. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01854-3 · Cited by 1,091
The endocannabinoid system and its therapeutic exploitation
Marzo, V. D., Bifulco, M., & Petrocellis, L. D. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1495 · Cited by 1,090
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,078
Control of pain initiation by endogenous cannabinoids
Calignano, A., Rana, G. L., Giuffrida, A., & Piomelli, D. (1998) · Nature · doi:10.1038/28393 · Cited by 1,069
Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration
Walter, L. M., Franklin, A., Witting, A., Wade, C. B., Xie, Y., Kunos, G., Mackie, K., & Stella, N. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01398.2003 · Cited by 674
HU-308: A specific agonist for CB 2 , a peripheral cannabinoid receptor
Hanus, L. O., Breuer, A., Tchilibon, S., Shiloah, S., Goldenberg, D., Horowitz, M., Pertwee, R. G., Ross, R. A., Mechoulam, R., & Fride, E. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.25.14228 · Cited by 581
Ibrahim, M. M., Porreca, F., Lai, J., Albrecht, P. J., Rice, F. L., Khodorova, A., Davar, G., Makriyannis, A., Vanderah, T. W., Mata, H. P., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409888102 · Cited by 521
CANNABINOID RECEPTORS AS THERAPEUTIC TARGETS
Mackie, K. (2005) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141254 · Cited by 518
Guide to Receptors and Channels (GRAC), 3rd edition
Alexander, S. P. H., Mathie, A. A., & Peters, J. A. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707746 · Cited by 510
Pharmacology of Cannabinoid Receptors
Howlett, A. C. (1995) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.003135 · Cited by 493
Ibrahim, M. M., Deng, H., Zvonok, A., Cockayne, D. A., Kwan, J., Mata, H. P., Vanderah, T. W., Lai, J., Porreca, F., Makriyannis, A., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834309100 · Cited by 491
Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain
Guo, W., Wang, H., Watanabe, M., Shimizu, K., Zou, S., LaGraize, S. C., Wei, F., Dubner, R. A., & Ren, K. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0176-07.2007 · Cited by 480
Does the right side know what the left is doing?
Koltzenburg, M., Wall, P. D., & McMahon, S. B. (1999) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01302-2 · Cited by 456
Guindon, J., & Hohmann, A. G. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707531 · Cited by 423
Zhang, J., Hoffert, C., Vu, H. K., Groblewski, T., Ahmad, S., & O'Donnell, D. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02704.x · Cited by 419
CB2 cannabinoid receptor-mediated peripheral antinociception
Malan, P. T., Ibrahim, M. M., Deng, H., Liu, Q., Mata, H. P., Vanderah, T., Porreca, F., & Makriyannis, A. (2001) · Pain · doi:10.1016/s0304-3959(01)00321-9 · Cited by 391
Carlisle, S. J., Marciano‐Cabral, F., Staab, A., LUDWICK, C., & Cabral, G. A. (2002) · International Immunopharmacology · doi:10.1016/s1567-5769(01)00147-3 · Cited by 347
Núñez, E., Benito, C., Pazos, M. R., Barbáchano, A., Fajardo, O., González, S. R., Tolón, R. M., & Romero, J. (2004) · Synapse · doi:10.1002/syn.20050 · Cited by 346
Cannabinoid CB 2 receptors in human brain inflammation
Benito, C., Tolón, R. M., Pazos, M. R., Núñez, E., Castillo, A. I., & Romero, J. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707505 · Cited by 304
CB2 receptor-mediated antihyperalgesia: possible direct involvement of neural mechanisms
Beltramo, M., Bernardini, N., Bertorelli, R., Campanella, M., Nicolussi, E., Fredduzzi, S., & Reggiani, A. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04684.x · Cited by 290
Valenzano, K. J., Tafesse, L., Lee, G., Harrison, J. E., Boulet, J. M., Gottshall, S. L., Mark, L., Pearson, M. S., Miller, W., Shan, S., et al. (2005) · Neuropharmacology · doi:10.1016/j.neuropharm.2004.12.008 · Cited by 288
Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons
Wotherspoon, G., Fox, A., McIntyre, P., Colley, S., Bevan, S., & Winter, J. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.06.009 · Cited by 251
Cannabinoid receptors in microglia of the central nervous system: immune functional relevance
Cabral, G. A., & Marciano‐Cabral, F. (2005) · Journal of Leukocyte Biology · doi:10.1189/jlb.0405216 · Cited by 241
CB cannabinoid receptor agonists: pain relief without psychoactive effects?
MALANJR, T., IBRAHIM, M., LAI, J., Vanderah, T. W., Makriyannis, A., & Porreca, F. (2003) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(02)00004-8 · Cited by 226
CB2 cannabinoid receptor mediation of antinociception
Ibrahim, M. M., Rude, M. L., Stagg, N. J., Mata, H. P., Lai, J. Y., Vanderah, T. W., Porreca, F., Buckley, N. E., Makriyannis, A., & Malan, P. T. (2006) · Pain · doi:10.1016/j.pain.2005.12.018 · Cited by 173
Romero-Sandoval, A., Nutile-McMenemy, N., & DeLeo, J. A. (2008) · Anesthesiology · doi:10.1097/aln.0b013e318167af74 · Cited by 168
Sagar, D. R., Kelly, S., Millns, P. J., O'Shaughnessey, C. T., Kendall, D. A., & Chapman, V. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04206.x · Cited by 154
SR 141716A, a cannabinoid receptor antagonist, produces hyperalgesia in untreated mice
Richardson, J. D., Aanonsen, L., & Hargreaves, K. (1997) · European Journal of Pharmacology · doi:10.1016/s0014-2999(96)00952-1 · Cited by 149
Yao, B. B., Hsieh, G. C., Frost, J. M., Fan, Y., Garrison, T. R., Daza, A. V., Grayson, G. K., Zhu, C. Z., Pai, M., Chandran, P., et al. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707568 · Cited by 140
Self-citationWalczak, J.-S., Pichette, V., Leblond, F., Desbiens, K., & Beaulieu, P. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.02.010 · Cited by 133
Whiteside, G. T., Lee, G. P., & Valenzano, K. J. (2007) · Current Medicinal Chemistry · doi:10.2174/092986707780363023 · Cited by 132
Hohmann, A. G., Farthing, J. N., Zvonok, A. M., & Makriyannis, A. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.060079 · Cited by 124
Romero-Sandoval, A. E., & Eisenach, J. C. (2007) · Anesthesiology · doi:10.1097/01.anes.0000264765.33673.6c · Cited by 122
Nackley, A. G., Zvonok, A. M., Makriyannis, A., & Hohmann, A. G. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00886.2003 · Cited by 112
Gutierrez, T., Farthing, J. N., Zvonok, A. M., Makriyannis, A., & Hohmann, A. G. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706984 · Cited by 108
Elmes, S. J. R., Winyard, L. A., Medhurst, S. J., Clayton, N. M., Wilson, A. W., Kendall, D. A., & Chapman, V. (2005) · Pain · doi:10.1016/j.pain.2005.09.005 · Cited by 97
Whiteside, G. T., Gottshall, S. L., Boulet, J. M., Chaffer, S. M., Harrison, J., Pearson, M. S., Turchin, P. I., Mark, L., Garrison, A. E., & Valenzano, K. J. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.10.043 · Cited by 94
Bingham, B., JONES, P. G., Uveges, A. J., Kotnis, S., Lu, P., Smith, V. A., Sun, S., Resnick, L., Chlenov, M., He, Y., et al. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707303 · Cited by 93
Yao, B. B., Hsieh, G., Daza, A. V., Fan, Y., Grayson, G. K., Garrison, T. R., El Kouhen, O., Hooker, B. A., Pai, M., Wensink, E. J., et al. (2009) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.145011 · Cited by 92 · cited 3×
“A-836339 is shown to exhibit relatively few off-target interactions (Yao et al., 2009), which is in contrast to the CB2-selective ligand AM1241 that exhibits significant radioligand binding affinity to a large number of additional GPCR and ion channel targets (Yao et al., 2008).”
BackgroundInfluentialSelf-citationWalczak, J., Pichette, V., Leblond, F., Desbiens, K., & Beaulieu, P. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20821 · Cited by 62
Giblin, G. M. P., Billinton, A., Briggs, M. A., Brown, A. J., Chessell, I. P., Clayton, N. M., Eatherton, A. J., Goldsmith, P., Haslam, C. P., Johnson, M. R., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm9009857 · Cited by 55
Lever, I. J., & Malcangio, M. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704506 · Cited by 49
Rueter, L. E., Kohlhaas, K. L., Curzon, P., Surowy, C. S., & Meyer, M. D. (2003) · Pain · doi:10.1016/s0304-3959(02)00455-4 · Cited by 42
Self-citation
Cited by
Sorted by citations
Cannabinoids and Pain: New Insights From Old Molecules
Vučković, S., Srebro, D., Vujović, K. S., Vučetić, Č., & Prostran, M. S. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01259 · Cited by 440
Donvito, G., Nass, S. R., Wilkerson, J. L., Curry, Z. A., Schurman, L. D., Kinsey, S. G., & Lichtman, A. H. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.204 · Cited by 301
CB2 Cannabinoid Receptors as a Therapeutic Target—What Does the Future Hold?
Dhopeshwarkar, A., & Mackie, K. (2014) · Molecular Pharmacology · doi:10.1124/mol.114.094649 · Cited by 266
“tion (Maresz et al., 2005; Hsieh et al., 2011).”
An overview of the cannabinoid type 2 receptor system and its therapeutic potential
Bie, B., Wu, J., Foss, J. F., & Naguib, M. (2018) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000616 · Cited by 230
Deng, L., Guindon, J., Cornett, B., Makriyannis, A., Mackie, K., & Hohmann, A. G. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.04.009 · Cited by 200
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
