doi: 10.1016/j.neuropharm.2021.108712.
- PMID: 34274349
- DOI: 10.1016/j.neuropharm.2021.108712
Abstract
The incidence of chronic pain is high in the general population and it is closely related to anxiety disorders, which promote negative effects on the quality of life. The cannabinoid system has essential participation in the pain sensitivity circuit. In this perspective, cannabidiol (CBD) is considered a promising strategy for treating neuropathic pain. Our study aimed to evaluate the effects of sub-chronic systemic treatment with CBD (0.3, 3, 10, or 30 mg/kg, i.p.) in male in rats submitted to chronic constriction injury of the sciatic nerve (CCI) or not (SHAM) and assessed in nociceptive tests (von Frey, acetone, and hot plate, three days CBD’s treatment) and in the open field test (OFT, two days CBD’s treatment). We performed a screening immunoreactivity of CB1 and TRPV1 receptors in cortical and limbic regions tissues, which were collected after 1.5 h of behavioral tests on the 24th experimental day. This study presents a dose-response curve to understand better the effects of low doses (3 mg/kg) on CBD’s antiallodynic and anxiolytic effects. Also, low doses of CBD were able to (1) reverse mechanical and thermal allodynia (cold) and hyperalgesia, (2) reverse anxious behaviors (reduction of the % of grooming and freezing time, and increase of the % of center time in the OFT) induced by chronic pain. The peripheral neuropathy promoted the increase in the expression of CB1 and TRPV1 receptors in the anterior cingulate cortex (ACC), anterior insular cortex (AIC), basolateral amygdala (BLA), dorsal hippocampus (DH), and ventral hippocampus (VH). CBD potentiated this effect in the ACC, AIC, BLA, DH, and VH regions. These results provide substantial evidence of the role of the ACC-AIC-BLA corticolimbic circuit, and BLA-VH for pain regulation. These results can be clinically relevant since they contribute to the evidence of CBD’s beneficial effects on treating chronic pain and associated comorbidities such as anxiety.
Keywords: Basolateral amygdala, Cannabidiol, Chronic pain, Cingulate cortex, Hippocampus, Insular cortex
Copyright © 2021. Published by Elsevier Ltd.
Conflict of interest statement
Declaration of competing interest J.A.S.C., J.E.C.H., and A.W.Z. are coinventors of the patent ‘‘Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,’’ Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi A.W., Kapczinski F, Hallak J.E.C, Guimarâes F.S., Crippa J.A.S., Breuer A). The University of São Paulo has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1). The University of São Paulo has an agreement with Prati Donaduzzi Pharm to ‘‘develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders.’’ J.A.S.C, J.E.C.H, and A.W.Z. are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same”, INPI on September 16, 2016 (BR 112018005423-2). J.A.S.C. is a member of the International Advisory Board of the Australian Center for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council (NHMRC). J.A.S.C. and J.E.C.H. have received travel support to scientific meetings and personal consultation fees from BSPG-Pharm. J.A.S.C. A.W.Z., and J.E.C.H. are recipients of Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) productivity fellowships (1A). J.A.S.C. receives a grant from the University Global Partnership Network (UGPN) – Global priorities in cannabinoid research excellence program. J.A.S.C. is a member of the International Advisory Board of the Australian Center for Cannabinoid Clinical and Research Excellence (ACRE – National Health and Medical Research Council, NHMRC). The other authors declare that they have no competing interests.
