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Brain Res. 2019 Mar 18. pii: S0006-8993(19)30153-2. doi: 10.1016/j.brainres.2019.03.014. [Epub ahead of print]

Cannabidiol attenuates mechanical allodynia in streptozotocin-induced diabetic rats via serotonergic system activation through 5-HT1A receptors.

Author information

1
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil.
2
Institute of Neurosciences and Behavior (INeC) and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
3
Institute of Neurosciences and Behavior (INeC) and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirão Preto, São Paulo, Brazil; Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Institute of Science and Technology for Translational Medicine (INCT-TM-CNPq), Ribeirão Preto, São Paulo, Brazil.
4
Department of Neuroscience and Behavioral Sciences, Ribeirão Preto Medical School, University of São Paulo, Brazil; National Institute of Science and Technology for Translational Medicine (INCT-TM-CNPq), Ribeirão Preto, São Paulo, Brazil.
5
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil; Institute of Neurosciences and Behavior (INeC) and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
6
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil; Institute of Neurosciences and Behavior (INeC) and Laboratory of Neuropsychopharmacology of Faculty of Philosophy, Sciences and Letters of University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: joice.cunha@ufpr.br.

Abstract

Most diabetic patients describe moderate to severe pain symptoms whose pharmacological treatment is palliative and poorly effective. Cannabidiol (CBD) has shown promising results in painful conditions. Then, we aimed to investigate the potential antinociceptive effect of CBD over the mechanical allodynia in streptozotocin-induced diabetic (DBT) rats, as well as its involved mechanisms. Wistar adult male diabetic rats were treated acutely or sub-chronically (for 14 days) with CBD (0.1, 0.3 or 3 mg/Kg, intraperitoneal; i.p.) and had their mechanical threshold assessed using the electronic Von Frey. Acute treatment with CBD (at doses of 0.3 and 3 mg/Kg) exerted a significant anti-allodynic effect, which is not associated with locomotor impairment. The antinociceptive effect of CBD (3 mg/Kg) was not altered by the pre-treatment with CB1 or CB2 receptor antagonists (AM251 and AM630; respectively; both at a dose of 1 mg/kg, i.p.) nor by glycine receptor antagonist (strychnine hydrochloride, 10 μg/rat, intrathecal, i.t.). However, this effect was completely prevented by the pre-treatment with the selective 5-HT1A receptor antagonist WAY 100135 (3 μg/rat, i.t.). Sub-chronic treatment with CBD (0.3 or 3 mg/Kg) induced a sustained attenuation of the mechanical allodynia in DBT rats. DBT rats presented significantly lower spinal cord levels of serotonin, which was prevented by the daily treatment with CBD (0.3 mg/Kg). Taken together, our data suggest that CBD may be effective in the treatment of painful diabetic neuropathy and this effect seems to be potentially mediated by the serotonergic system activation through 5-HT1A receptors.

KEYWORDS:

Cannabinoid receptors; Cannabinoids; Diabetes; Neuropathic pain; Serotonin

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