Antiallodynic effect of PhAR ‐DBH‐Me involves cannabinoid and TRPV1 receptors

AbstractThe antiallodynic effect of PhAR ‐DBH‐Me was evaluated on two models of neuropathic pain, and the potential roles of CB1, CB2, and TRPV1 receptors as molecular targets of PhAR‐DBH‐Me were studied. Female Wistar rats were submitted to L5/L6 spinal nerve ligation (SNL) or repeated doses of cisplatin (0.1 mg/kg, i.p.) to indu ce experimental neuropathy. Then, tactile allodynia was determined, and animals were treated with logarithmic doses of PhAR‐DBH‐Me (3.2‐100 mg/kg, i.p.). To evaluate the mechanism of action of PhAR‐DBH‐Me, in silico studies using crystallized structures of CB1, CB2, and TRPV1 receptors we re performed. To corroborate the computational insights, animals were intraperitoneally administrated with antagonists for CB1 (AM‐251, 3 mg/kg), CB2 (AM‐630, 1 mg/kg), and TRPV1 receptors (capsazepine, 3 mg/kg), 15 min before to PhAR‐DBH‐Me (100 mg/kg) administration. Vagal stimulation evoked on striated muscle contraction in esophagus, was used to elicited pharmacological response of PhAR‐DBH‐ME on nervous tissue. Systemic administration of PhAR‐DBH‐Me reduced the SNL‐ and cisplatin‐induced allodynia. Docking studies suggested that PhAR‐DBH‐Me acts as an agonist for CB1, CB2, and TRPV1 receptors, with similar affinity to the endogenous ligand anandamide. Moreover antiallodynic effect of PhAR‐DBH‐Me was partially prevented by administration of AM‐251 and AM‐630, and completely prevented by capsazepine. Final...

Source: Pharmacology Research and Perspectives - September 22, 2020 Category: Drugs & Pharmacology Authors: Geovanna Nallely Qui ñonez‐Bastidas, Oscar Palomino‐Hernández, Manuel López‐Ortíz, Héctor Isaac Rocha‐González, Gloria Melisa González‐Anduaga, Ignacio Regla, Andrés Navarrete Tags: ORIGINAL ARTICLE Source Type: research