TRPV1 desensitization by Capsicum annuum as a potential mode of action of the medicinal product Tonsipret

Tonsipret is a homeopathic medicinal product for the treatment of acute inflammation of the throat and tonsils. It contains the active ingredients Phytolacca americana, Guaiacum and Capsicum annuum with the main constituent capsaicin.

We investigated the potential mode of action underlying the intended analgesic effect of Tonsipret and its Capsicum ingredient in in vitro assays on substance P release as well as activation and desensitization of the human pain receptor TRPV1. In an in vitro primary neuron model, Capsicum annuum mother tincture was tested for stimulation of substance P release. The release of substance P was measured with ELISA. Capsicum annuum mother tincture was tested for the capability to activate the human pain receptor TRPV1 overexpressed on CHO-cells. TRPV1 activation was assessed as Ca²⁺ increase.

The desensitization or tachyphylaxis of TRPV1 channel by the active ingredient mixture contained in Tonsipret was determined with patch-clamp measurement in HEK293T cells transfected with TRPV1. Capsicum mother tincture at 0.03, 0.06, and 0.12% was able to induce the release of substance P from sensory neurons. We also detected an activation of the pain receptor TRPV1. The Capsicum annuum mother tincture exerted TRPV1 agonist activity with an EC₅₀= 0.0034%. Repeated administration of a dilution of the active ingredient mixture contained in Tonsipret produced an early activation of TRPV1, which subsequently led to desensitization to capsaicin challenge. The concentration of the active ingredient mixture used experimentally corresponded to the local concentrations of Tonsipret achievable in saliva during clinical use. The results indicate a local analgesic effect of Tonsipret by desensitization of the human pain receptor TRPV1.

Keywords: Capsaicin, TRPV1, tachyphylaxis.