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Studies have shown high comorbidity of anxiety disorder and chronic pain; generalized anxiety disorder (GAD) and neuropathic pain are among these pathologies. Cannabidiol (CBD) has been considered a promising treatment for these conditions. This study investigated whether chronic systemic treatment with CBD alters pain in high- (CHF) and low-freezing (CLF) Carioca rats (GAD model) and control rats (CTL) submitted to chronic neuropathic pain. The rats were evaluated in the sensory aspects (von Frey, acetone, and hot plate tests) before the chronic constriction injury of the ischiatic nerve (CCI) or not (SHAM) and on days 13 and 23 after surgery. Chronic treatment with CBD (5 mg/kg daily) was used for ten days, starting the 14th day after surgery. The open field test on the 22nd also evaluated locomotion and anxiety-like behavior. CBD treatment had an anti-allodynic effect on the mechanical and thermal threshold in all lineages; however, these effects were lower in the CHF and CLF lineages. Considering emotional evaluation, we observed an anxiolytic effect in CTL+CCI and CHF+CCI after CBD treatment and increased mobility in CLF+SHAM rats. These results suggest that the CBD mechanical anti-allodynic and emotional effects can depend on anxiety level.

Epilepsies are neurological disorders characterized by chronic seizures and their related neuropsychiatric comorbidities, such as anxiety. The Transient Receptor Potential Vanilloid type-1 (TRPV1) channel has been implicated in the modulation of seizures and anxiety-like behaviors in preclinical models. Here, we investigated the impact of chronic epileptic seizures in anxiety-like behavior and TRPV1 channels expression in a genetic model of epilepsy, the Wistar Audiogenic Rat (WAR) strain. WARs were submitted to audiogenic kindling (AK), a preclinical model of temporal lobe epilepsy (TLE) and behavioral tests were performed in the open-field (OF), and light-dark box (LDB) tests 24 h after AK. WARs displayed increased anxiety-like behavior and TRPV1R expression in the hippocampal CA1 area and basolateral amygdala nucleus (BLA) when compared to control Wistar rats. Chronic seizures increased anxiety-like behaviors and TRPV1 and FosB expression in limbic and brainstem structures involved with epilepsy and anxiety comorbidity, such as the hippocampus, superior colliculus, and periaqueductal gray matter. Therefore, these results highlight previously unrecognized alterations in TRPV1 expression in brain structures involved with TLE and anxiogenic-like behaviors in a genetic model of epilepsy, the WAR strain, supporting an important role of TRPV1 in the modulation of neurological disorders and associated neuropsychiatric comorbidities.