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Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats

Petrosino, Stefania, Palazzo, Enza, de Novellis, Vito, Bisogno, Tiziana, Rossi, Francesco, Maione, Sabatino, Di Marzo, Vincenzo·2007·Neuropharmacology

DOI 10.1016/j.neuropharm.2006.08.011

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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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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)
ORCID: Petrosino, Stefania
Bisogno, Tiziana
Rossi, Francesco
Maione, Sabatino
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2007-02
Volume: 52
Issue: 2
Pages: 415-422
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2006.08.011
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Changes in spinal and supraspinal endocannabinoid levels in neuropathic rats

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