Cannabidiol effectively reverses mechanical and thermal allodynia, hyperalgesia, and anxious behaviors in a neuropathic pain model: Possible role of CB1 and TRPV1 receptors

Author(s)

Silva-Cardoso, Gleice K. ^{[1, 2]} ; Lazarini-Lopes, Willian ^{[2, 3]} ; Hallak, Jaime E. ^{[2, 3]} ; Crippa, Jose A. ^{[2, 3]} ; Zuardi, Antonio W. ^{[2, 3]} ; Garcia-Cairasco, Norberto ^{[3, 4]} ; Leite-Panissi, Christie R. A. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Fac Philosophy Sci & Letters Ribeiao Preto, Dept Psychol, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Natl Inst Translat Med INCT TM CNPq, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurosci & Behav Sci, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Physiol, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Neuropharmacology; v. 197, OCT 1 2021.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 19/05957-8 - Epilepsies and neuropsyquiatric comorbidities: characterization of the effects of the treatment with cannabidiol and HUF-101 in in vivo and in vitro experimental models
• Grantee: Norberto Garcia Cairasco
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/06877-5 - Systemic treatment with canabidiol in a neuropathic pain model: evaluation of the sensorial-discriminative and emotional-motivacional components pain sensitivity
• Grantee: Gleice Kelli Ribeiro da Silva Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/50891-1 - INCT 2014: Translational Medicine
• Grantee: Jaime Eduardo Cecilio Hallak
• Support Opportunities: Research Projects - Thematic Grants