The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats
Abstract
Recent studies have shown that activation of the cannabinoid CB(1) receptor by synthetic agonists, and pharmacological elevation of endocannabinoid levels, suppress hyperalgesia and allodynia in animal models of neuropathic pain. However, the concentrations of endocannabinoids in the nervous tissues involved in pain transmission during neuropathic pain have never been measured. Here we have determined the levels of anandamide and 2-arachidonoylglycerol (2-AG), as well as of the analgesic anandamide congener, palmitoylethanolamide (PEA), in three brain areas involved in nociception, i.e. the dorsal raphe (DR), periaqueductal grey (PAG) and rostral ventral medulla (RVM), as well as in the spinal cord (SC), following chronic constriction injury (CCI) of the sciatic nerve in the rat, in comparison with sham-operated rats. After 3 days from CCI, anandamide or 2-AG levels were significantly enhanced only in the SC or PAG, respectively. After 7 days from CCI, when thermal hyperalgesia and mechanical allodynia are maximal, a strong (1.3-3-fold) increase of both anandamide and 2-AG levels was observed in the PAG, RVM and SC. At this time point, anandamide, but not 2-AG, levels were also enhanced in the DR. PEA levels were significantly decreased in the SC after 3 days, and in the DR and RVM after 7 days from CCI. These data indicate that anandamide and 2-AG, operating at both spinal and supra-spinal levels, are up-regulated during CCI of the sciatic nerve, possibly to inhibit pain. Yet to be developed substances that inhibit both endocannabinoid and PEA inactivation might be useful for the treatment of neuropathic pain.
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“CCI increases AEA and 2-AG levels in the PAG and RVM, sites implicated in the descending modulation of pain.56”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [56]
Citations
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633
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
The endogenous cannabinoid system controls extinction of aversive memories
Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., Hermann, H., Tang, J., Hofmann, C., Zieglgänsberger, W., et al. (2002) · Nature · doi:10.1038/nature00839 · Cited by 1,728
Self-citationBisogno, 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
Self-citationMezey, É., Tóth, Z. E., Cortright, D. N., Arzubi, M. K., Krause, J. E., Elde, R., Guo, A., Blumberg, P. M., & Szallasi, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3655 · Cited by 850
An endocannabinoid mechanism for stress-induced analgesia
Hohmann, A. G., Suplita, R. L., Bolton, N. M., Neely, M. H., Fegley, D., Mangieri, R., Krey, J. F., Michael Walker, J., Holmes, P. V., Crystal, J. D., et al. (2005) · Nature · doi:10.1038/nature03658 · Cited by 778
Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis
Rog, D. J., Nurmikko, T. J., Friede, T., & Young, C. A. (2005) · Neurology · doi:10.1212/01.wnl.0000176753.45410.8b · Cited by 679
Pain modulation by release of the endogenous cannabinoid anandamide
Walker, J. M., Huang, S. M., Strangman, N. M., Tsou, K., & Sañudo-Peña, M. C. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.21.12198 · Cited by 486
Descending modulation in persistent pain: an update
Ren, K., & Dubner, R. A. (2002) · Pain · doi:10.1016/s0304-3959(02)00368-8 · Cited by 427
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
Research works printed but not linked: 2
- Costa, B., Colleoni, M., Trovato, A.E., Conti, S., Pomelli, F., Franke, C., 2005. Anandamide uptake and hydrolysis as targets for the treatment of neuropathic pain: effect of AM404 and URB597 in rats with chronic constriction injury of the sciatic nerve. XV Symposium on the Cannabinoids, Clearwater Beach, FL, 24–29 June 2005, p. 33.
- Costa, B., Comelli, F., Colleoni, M., Giagnoni, G., 2006. Effect of CB1/TRPV1 agonist, arvanil, in acute inflammation and in persistent inflammatory and neuropathic pain. XVI Symposium on the Cannabinoids, Tihany, Hungary, 24–29 June 2006, p. 38.
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Marzo, V. D. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2553 · Cited by 822
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Saturnino, C., Popolo, A., Ramunno, A., Adesso, S., Pecoraro, M., Plutino, M. R., Rizzato, S., Albinati, A., Marzocco, S., Sala, M., et al. (2017) · Molecules · doi:10.3390/molecules22040616 · Cited by 451
Cannabinoids and Pain: New Insights From Old Molecules
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Metadata
- Authors
- Petrosino, S., Palazzo, E., de Novellis, V., Bisogno, T., Rossi, F., Maione, S., & Di Marzo, V.
- Affiliations
- Istituto di Chimica Biomolecolare (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2007-02
- Volume
- 52
- Issue
- 2
- Pages
- 415-422
- ISSN
- 0028-3908 (ISSN-L)
- OpenAlex
- W2061301719
- Cited by
- 227
- References
- 46
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 5 · 2023: 5 · 2022: 12 · 2021: 7 · 2020: 16 · 2019: 10 · 2018: 7 · 2017: 14 · 2016: 7 · 2015: 14 · 2014: 11 · 2013: 18 · 2012: 15
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
- Keywords
- endocannabinoids, neuropathic pain, anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, chronic constriction injury, sciatic nerve, spinal cord, dorsal raphe nucleus, periaqueductal gray, rostral ventrolateral medulla, thermal hyperalgesia, mechanical allodynia, CB1 receptor, analgesia
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Disease Models, Animal, Male, Pain Measurement, Reaction Time, Sciatica, Mass Spectrometry, Spinal Cord, Time Factors, Rats, Wistar, Rats, Cannabinoid Receptor Modulators, Endocannabinoids
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