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Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease.
Neuropharmacology. 2020 02; 163:107808.N

Abstract

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.

Authors+Show Affiliations

Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14040-904, Brazil; Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil.Department of Neuroscience, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil.Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil.Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14040-904, Brazil; Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil; Department of Neuroscience, School of Medicine of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14049-900, Brazil.Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14040-904, Brazil. Electronic address: marizabortolanza@usp.br.Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, SP, 14040-904, Brazil. Electronic address: juniormb@usp.br.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31706993

Citation

Crivelaro do Nascimento, Glauce, et al. "Cannabidiol Increases the Nociceptive Threshold in a Preclinical Model of Parkinson's Disease." Neuropharmacology, vol. 163, 2020, p. 107808.
Crivelaro do Nascimento G, Ferrari DP, Guimaraes FS, et al. Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease. Neuropharmacology. 2020;163:107808.
Crivelaro do Nascimento, G., Ferrari, D. P., Guimaraes, F. S., Del Bel, E. A., Bortolanza, M., & Ferreira-Junior, N. C. (2020). Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease. Neuropharmacology, 163, 107808. https://doi.org/10.1016/j.neuropharm.2019.107808
Crivelaro do Nascimento G, et al. Cannabidiol Increases the Nociceptive Threshold in a Preclinical Model of Parkinson's Disease. Neuropharmacology. 2020;163:107808. PubMed PMID: 31706993.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol increases the nociceptive threshold in a preclinical model of Parkinson's disease. AU - Crivelaro do Nascimento,Glauce, AU - Ferrari,Daniele Pereira, AU - Guimaraes,Francisco Silveira, AU - Del Bel,Elaine Aparecida, AU - Bortolanza,Mariza, AU - Ferreira-Junior,Nilson Carlos, Y1 - 2019/11/07/ PY - 2019/05/22/received PY - 2019/09/11/revised PY - 2019/10/02/accepted PY - 2019/11/11/pubmed PY - 2021/1/5/medline PY - 2019/11/11/entrez KW - 6-Hydroxydopamine KW - Anandamide KW - Cannabidiol KW - Cannabinoid receptors KW - Pain KW - Parkinson's disease KW - Transient receptor potential vanilloid type 1 SP - 107808 EP - 107808 JF - Neuropharmacology JO - Neuropharmacology VL - 163 N2 - Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/31706993/Cannabidiol_increases_the_nociceptive_threshold_in_a_preclinical_model_of_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -