Effects of Salicornia-Based Skin Cream Application on Healthy Humans’ Experimental Model of Pain and Itching

Halophyte plants are salt-tolerant and are acclimated for growth in saline soils such as along coastal areas. Among the halophytes, the Salicornia species have been used as both folk medicine and functional food for many years due to their high levels of bioactive compounds with supposed anti-inflammatory and antioxidative effects. However, the properties of Salicornia bioactive extracts on pain and itching still remain unclear. In this study, 30 healthy volunteers were randomized to treatments with 10% Salicornia-based cream or placebo cream for 24 or 48 h. On day 0, and 24 or 48 h post cream application, cold/heat detection and pain thresholds, mechanical pain thresholds and sensitivity, trans-epidermal water loss, histamine- and cowhage-evoked itch, and micro-vascular reactivity (neurogenic inflammation) were assessed to evaluate the analgesic, anti-pruritogenic and vasomotor effects. Skin permeability was reduced in the Salicornia-treated area for 48 h compared with 24 h application (p-value < 0.05). After 48 h of application, a decrease in mechanical-evoked itching (hyperkinesis) compared with 24 h treatment (p-value < 0.05) and increased warm detection and heat pain thresholds (p-value < 0.05) was found. Histamine-induced neurogenic inflammation showed a significant reduction in the cream-treated areas after 48 h compared with 24 h (p-value < 0.05). The results of this study indicate the overall inhibitory effect of Salicornia on hyperkinesis (mechanically evoked itch), the analgesic effect on thermal sensation, and modulation of the skin barrier architecture. Further studies are needed for the assessment of the long-term effects

Antagonizing trpa1 receptors counteracts non-histaminergic itch in humans

Background and aims: Chronic itch is a common symptom of several pathological conditions with a lifetime prevalence of about 20%. In most conditions chronic itch follows a histamine-independent pathway, involving a subgroup of polymodal C-fibers that can be experimentally activated by the application of BAM8-22, an agonist of Mas-related G protein-coupled receptor X1 (MrgprX1). Moreover, the TRPA1 receptor downstream activation can likewise be involved in non-histaminergic itch generation. This study aimed to evaluate the interaction between MrgprX1 and TRPA1 by modulating BAM8-22-induced non-histaminergic itch by TRPA1 antagonist A-967079.Methods: Twenty-two healthy subjects were randomized, using a single-blinded protocol. Four areas on the forearms were selected and treated as follows: vehicle+BAM8-22, A-967079+BAM8-22, A-967079+BAM8-22 (applied after 5 minutes), and A-967079+inactivated cowhage spicules. A-967079 (0.5 mg/ml) and vehicle were intradermally injected (0.1 ml), while BAM8-22 was applied through inactivated cowhage spicules coated with while BAM8-22 (2 mg/ml). After spicules application, itch intensity was scored with a visual analog scale for 9 minutes followed by the assessment of the mechanically evoked itch.Results: Itch evoked by ‘A-967079+BAM8-22 (after 5 min)’ resulted in a lower intensity than ‘vehicle+BAM8-22’ (p&lt;0.05). Moreover, the mechanically evoked itch was lower in ‘A-967079+BAM8-22 (after 5 min)’ and ‘A-967079+inativated spicules’ areas compared to ‘vehicle+BAM8-22’ (p&lt;0.05).Conclusions: A-967079 reduced the itch intensity and the mechanically evoked itch in BAM8-22-induced non-histaminergic itch. This study confirmed the involvement of TRPA1 receptors in the signal pathway of non-histaminergic itch generation and hence the block of TRPA1 receptors can be a promising option for treating chronic itch.</div