Background & Aims
Trigeminal neuralgia (TN) is a classical condition of orofacial neuropathic pain that significantly impacts patients’ quality of life, affecting their psychological, physical, and social well-being, and interfering with daily activities. The pathophysiology of neuropathic pain involves functional changes in both the central nervous system (CNS) and the peripheral nervous system (PNS), along with neuroimmune modifications. The hypersensitivity of these systems compromises sensory responses, leading to allodynia and hyperalgesia. Relief from these hypersensitive reactions has been associated with the modulation of transient receptor potential vanilloid type 1 (TRPV1) in the trigeminal spinal nucleus. The treatment of TN poses a considerable therapeutic challenge. Carbamazepine (CBZ), an anticonvulsant, is the most prescribed medication for TN. However, its ineffectiveness in some cases has been described, and the majority of patients experience at least one side effect.
Methods
To investigate the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (formerly HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. CBD, PECS-101, and Carbamazepine (3, 10, 30 mg/kg i.p) were administered once daily for seven days. Nociception was evaluated using Von Frey and Formalin tests. Motor impairment was evaluated by the rotarod test. In a pharmacological approach, we combined the selective TRPV1 antagonist (capsazepine-CPZ – 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg). Animals received CBD treatment once daily for seven consecutive days, and CPZ (5 mg/kg) was administered 30 minutes before CBD administration during the last three days of treatment. Von Frey and Formalin tests were also assessed. Tissue samples from the caudal part of the spinal trigeminal nucleus were collected for the analysis of TRPV1 protein expression using western blotting.
Results
After seven days of treatment, CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), and carbamazepine (10 and 30 mg/kg) demonstrated efficacy in reducing allodynia and hyperalgesia responses. Notably, unlike carbamazepine, CBD and PECS-101 did not induce motor activity impairment. Furthermore, CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) successfully reversed the increased expression of TRPV1 induced by IoN-CCI in the spinal trigeminal nucleus. Additionally, the combination of the selective TRPV1 antagonist (capsazepine-CPZ – 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) was effective in reversing IoN-CCI-induced allodynia and hyperalgesia responses, accompanied by a reduction in TRPV1 protein expression in the trigeminal spinal nucleus.
Conclusions
Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing in the central nervous system.
References
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Presenting Author
Daniela Maria Escobar Espinal
Poster Authors
Daniela Escobar
PhD
University of São Paulo
Lead Author
Maurício Dos Santos Pereira
PhD
Department of Basic and Oral Biology, School of Dentistry of Ribeirao Preto, University of Sao Paulo
Lead Author
Francisco Silveira Guimaraes
PhD
Department of Pharmacology, School of Medicine of Ribeirao Preto, University of Sao Paulo
Lead Author
Elaine Del Bel
Department of Physiology, School of Medicine of Ribeirao Preto, University of Sao Paulo
Lead Author
Glauce Nascimento
Faculdade de Odontologia de Ribeirão Preto da Universidade de São Paulo
Lead Author
Topics
- Treatment/Management: Cannabinoids and Cannabis