Cannabidiol modulates chronic neuropathic pain aversion behavior by attenuation of neuroinflammation markers and neuronal activity in the corticolimbic circuit in male Wistar rats

Author(s)

Silva-Cardoso, Gleice K. ; Lazarini-Lopes, Willian ; Primini, Eduardo Octaviano ; Hallak, Jaime E. ; Crippa, Jose A. ; Zuardi, Antonio W. ; Garcia-Cairasco, Norberto ; Leite-Panissi, Christie R. A.

• Document type: Journal article
• Source: Behavioural Brain Research; v. 452, p. 16-pg., 2023-08-24.

Abstract

Chronic neuropathic pain (CNP) is a vast world health problem often associated with the somatosensory domain. This conceptualization is problematic because, unlike most other sensations that are usually affectively neutral and may present emotional, affective, and cognitive impairments. Neuronal circuits that modulate pain can increase or decrease painful sensitivity based on several factors, including context and expectation. The objective of this study was to evaluate whether subchronic treatment with Cannabidiol (CBD; 0.3, 3, and 10 mg/kg intraperitoneal route -i.p., once a day for 3 days) could promote pain-conditioned reversal, in the conditioned place preference (CPP) test, in male Wistar rats submitted to chronic constriction injury (CCI) of the sciatic nerve. Then, we evaluated the expression of astrocytes and microglia in animals treated with CBD through the immunofluorescence technique. Our results demonstrated that CBD promoted the reversal of CPP at 3 and 10 mg/kg. In CCI animals, CBD was able to attenuate the increase in neuronal hyperactivity, measured by FosB protein expression, in the regions of the corticolimbic circuit: anterior cingulate cortex (ACC), complex baso-lateral amygdala (BLA), granular layer of the dentate gyrus (GrDG), and dorsal hippocampus (DH) -adjacent to subiculum (CA1). CBD also prevented the increased expression of GFAP and IBA-1 in CCI animals. We concluded that CBD effects on CNP are linked to the modulation of the aversive component of pain. These effects decrease chronic neuronal activation and inflammatory markers in regions of the corticolimbic circuit. (AU)

• FAPESP's process: 21/13622-6 - Assessing anxiety and painful hypersensitivity as comorbidities associated with Epilepsy: effects of cannabidiol treatment and the role of CB1, TRPV1 and 5-HT1A receptors
• Grantee: Willian Lazarini Lopes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/12439-3 - Cannabinoids in the amygdala-parabrachial circuit, and the regulation of pain
• Grantee: Gleice Kelli Ribeiro da Silva Cardoso
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 22/05471-0 - Pain modulation: effects of systemic treatment with cannabidiol and possible mechanisms
• Grantee: Christie Ramos Andrade Leite Panissi
• 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