Catecholamines reduce transient receptor potential vanilloid type 1 desensitization in cultured dorsal root ganglia...

Sympathetic nervous system and adrenergic receptors are involved in the modulation of dorsal root ganglia neuronal activity, with TRPV1 receptor as an important downstream effector. It is already known that adrenergic sensitization of TRPV1 receptors or catecholamine-induced TRPV1 upregulation are involved in increased excitability and pain via mainly α₁ adrenergic receptors, but it is not known if reduced TRPV1 desensitization is involved in this process, as well. Therefore, the aims of this study were to evaluate the effects of epinephrine and norepinephrine on TRPV1 desensitization induced by repeated applications of capsaicin and to assess what would be the involvement of the major α₁, α₂ and β adrenergic receptor subtypes. Using calcium microfluorimetry, the effects were evaluated by exposure to 1 μM epinephrine or 10 μM norepinephrine, alone or in the presence of adrenergic receptor inhibitors (phentolamine, prazosin and propranolol) before a 4^th capsaicin application in a series of 5 consecutive capsaicin applications. The results showed that both catecholamines produced significant reduction of TRPV1 desensitization, which was mediated by α₁, α₂ and β₂ receptors. This study completes the general information about TRPV1 sensitization via adrenergic stimulation and may open perspectives for novel pharmacological approaches in skin inflammatory disorders and pain therapy.