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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]
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Flagged first, then by citations
Research works printed but not linked: 2
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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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