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Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats
Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the man...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478794/ https://www.ncbi.nlm.nih.gov/pubmed/28680401 http://dx.doi.org/10.3389/fphar.2017.00391 |
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author | Genaro, Karina Fabris, Débora Arantes, Ana L. F. Zuardi, Antônio W. Crippa, José A. S. Prado, Wiliam A. |
author_facet | Genaro, Karina Fabris, Débora Arantes, Ana L. F. Zuardi, Antônio W. Crippa, José A. S. Prado, Wiliam A. |
author_sort | Genaro, Karina |
collection | PubMed |
description | Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection. Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg). Conditioned place preference (CPP) paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg) inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 μL) injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 μL) did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness. Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. In addition, the study gives further support to the notion that the sensorial and affective dimensions of pain may be differentially modulated by CBD. |
format | Online Article Text |
id | pubmed-5478794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54787942017-07-05 Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats Genaro, Karina Fabris, Débora Arantes, Ana L. F. Zuardi, Antônio W. Crippa, José A. S. Prado, Wiliam A. Front Pharmacol Pharmacology Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection. Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg). Conditioned place preference (CPP) paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg) inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 μL) injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 μL) did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness. Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. In addition, the study gives further support to the notion that the sensorial and affective dimensions of pain may be differentially modulated by CBD. Frontiers Media S.A. 2017-06-21 /pmc/articles/PMC5478794/ /pubmed/28680401 http://dx.doi.org/10.3389/fphar.2017.00391 Text en Copyright © 2017 Genaro, Fabris, Arantes, Zuardi, Crippa and Prado. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Genaro, Karina Fabris, Débora Arantes, Ana L. F. Zuardi, Antônio W. Crippa, José A. S. Prado, Wiliam A. Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title | Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title_full | Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title_fullStr | Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title_full_unstemmed | Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title_short | Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats |
title_sort | cannabidiol is a potential therapeutic for the affective-motivational dimension of incision pain in rats |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478794/ https://www.ncbi.nlm.nih.gov/pubmed/28680401 http://dx.doi.org/10.3389/fphar.2017.00391 |
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