The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Peripheral nerve injury induces cannabinoid receptor 2 protein expression in rat sensory neurons
Abstract
We have localized cannabinoid receptor 2 protein in rat and mouse somatic sensory nervous system, using an antibody that recognizes mouse cannabinoid receptor 2. Little or no cannabinoid receptor 2 immunoreactivity was found in sections of naive rat or mouse dorsal root ganglia or spinal cord. This was in accord with the lack of detectable cannabinoid receptor 2 mRNA in (dorsal root ganglion) neurons by in situ hybridization experiments described in the literature. However, we could detect cannabinoid receptor 2 immunoreactivity following unilateral nerve damage-either by sciatic nerve section, or by spinal nerve ligation. It was localized to the superficial laminae of the dorsal horn of the spinal cord, ipsilateral to the nerve damage, coincident with the area of termination of damaged afferents which was marked by loss of isolectin B4 binding. This upregulation was not seen in cannabinoid receptor 2 null mice. The cannabinoid receptor 2 protein in spinal cord appeared to be expressed on sensory neuron afferent terminals as it colocalized with two markers of damaged afferents, namely growth associated protein-43 and the neuropeptide galanin. Moreover, it did not colocalize with markers of activated microglial cells (OX-42) or astroglial cells (glial fibrillary acidic protein) in rat spinal cord. In the peripheral nerve, accumulation of cannabinoid receptor 2 immunoreactivity was seen in nerve sections proximal, but not distal, to the ligation site, suggesting transport down the nerve from the cell bodies. Although convincing cannabinoid receptor 2 immunoreactivity was seen in neither uninjured nor injured dorsal root ganglion neuron cell bodies in tissue sections, expression was detectable in isolated, cultured neurons that had received a prior axotomy in vivo. This clear demonstration of CB(2) receptors on sensory neurons suggests an additional cellular target for CB(2) agonist induced analgesia, at least in neuropathic models.
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“However, an upregulation of CB2 receptor immunoreactivity or mRNA is observed in sites implicated in nociceptive processing under conditions of induced neuropathy.17, 18”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [18]
In the citing paper
“Upregulation of CB2 receptor immunoreactivity on sensory afferent terminals in the spinal cord has also been reported following SNL.18”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [18]
In the citing paper
“These observations correspond to preclinical observations of cannabinoid receptor upregulation following nerve injury.18”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [18]
Citations
Cites
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GAP-43: an intrinsic determinant of neuronal development and plasticity
Benowitz, L. I., & Routtenberg, A. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)10072-2 · Cited by 1,329
Neuropathic pain and spinal microglia: a big problem from molecules in ‘small’ glia
Tsuda, M., Inoue, K., & Salter, M. W. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.12.002 · Cited by 795
Cannabinoid receptors and pain
Pertwee, R. G. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00031-9 · Cited by 741
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
Modulation of transmitter release via presynaptic cannabinoid receptors
Schlicker, E., & Kathmann, M. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01805-8 · Cited by 671
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
Cannabinoid receptors and their ligands
Pertwee, R. G., & Ross, R. A. (2002) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1054/plef.2001.0341 · Cited by 577
The cannabinoid system and immune modulation
Klein, T., Newton, C. A., Larsen, K. A., Lu, L. D., Perkins, I., Nong, L., & Friedman, H. P. (2003) · Journal of Leukocyte Biology · doi:10.1189/jlb.0303101 · Cited by 533
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
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Pertwee, R. G. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707442 · Cited by 2,047
Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. H., Marzo, V. D., Elphick, M. R., Greasley, P. J., Hansen, H. S., Kunos, G., Mackie, K., et al. (2010) · Pharmacological Reviews · doi:10.1124/pr.110.003004 · Cited by 1,666
CB2: a cannabinoid receptor with an identity crisis
Atwood, B. K., & Mackie, K. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00729.x · Cited by 659
Emerging strategies for exploiting cannabinoid receptor agonists as medicines
Pertwee, R. G. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00048.x · Cited by 436
Guindon, J., & Hohmann, A. G. (2008) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707531 · Cited by 423
Metadata
- Authors
- Wotherspoon, G., Fox, A., McIntyre, P., Colley, S., Bevan, S., & Winter, J.
- Affiliations
- Novartis (Switzerland) (CH)
- Corresponding author
- Winter, J.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 135
- Issue
- 1
- Pages
- 235-245
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2036912145
- Cited by
- 251
- References
- 47
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 9 · 2019: 9 · 2018: 10 · 2017: 9 · 2016: 11 · 2015: 6 · 2014: 16 · 2013: 14 · 2012: 11
- FWCI
- 12.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- CB2 receptor, peripheral nerve injury, neuropathic pain, sensory neurons, dorsal root ganglia, dorsal horn, sciatic nerve section, spinal nerve ligation, axotomy, galanin, growth-associated protein 43
- MeSH terms
- Animals, Astrocytes, Ganglia, Spinal, Cricetinae, Immunohistochemistry, Ligation, Male, Mice, Inbred C57BL, Neurons, Afferent, Pain, Peripheral Nervous System Diseases, Spinal Cord, Spinal Nerves, CHO Cells, Rats, Wistar, Microglia, DNA Primers, Mice, Knockout, Receptor, Cannabinoid, CB2, Mice, Rats, Peripheral Nerve Injuries
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