Introduction: Stimulated skin wrinkling (SSW) reflects the integrity of the autonomic nervous system, eccrine sweat glands, and microcirculation. Specific stimuli, as water immersion or mechanical pressure usually elicit it. This study explored the influence of some physical, chemical, sympathetic stimuli, and circadian cycle on SSW. Methods: Time required to achieve grade III finger wrinkling was assessed in 24 healthy adults. SSW induced by room-temperature filtered water (RTFW) for comparison across temperature variations: warm water (40°C) and iced water; tonicity: Distilled water and hypertonic saline (36% NaCl); pH variations: acidic and alkaline solution; oily medium: soybean oil; or pressure: immersion under hydrostatic pressure (30 cm water column). To evaluate the influence of sympathetic activity, SSW was assessed under caffeine stimulation: 30 min after ingestion of 60 mg caffeine (Ristretto espresso); diurnal variation: testing at 10 a.m. versus 10 p.m.; or ischemic influence: under sub-systolic ischemia induced by an arm cuff. Additionally, 12 participants underwent 10 min fingertip exposures to EMLA and room-temperature vinegar for comparison. Results: The time to reach grade III SSW under RTFW varied widely across the sample (from 2.1 to 37.0 min). The acidic solution reduced the time to SSW compared to RTFW (mean: 6.4 vs. 13.9 min; p < 0.01), with a more pronounced effect observed with a warm (40°C) acidic solution (4.0 vs. 15.5 min; p < 0.01). Hot water, distilled water, and 30 cm hydrostatic pressure stimulation shortened the time to SSW compared to RTFW (p < 0.01). No SSW was observed after 30 min of immersion in the oily medium, iced water, alkaline solution, hypertonic solution, or following ischemia. A circadian influence on SSW was also observed, with morning measurements resulting in a faster response than at night (10.4 vs. 14.6 min; p < 0.01). SSW was also accelerated after coffee consumption (6.1 vs. 10.5 min; p < 0.01). After 10 min of stimulation with either EMLA or vinegar, 75% of participants reached grade III SSW (p = 1.00). Conclusion: SSW is influenced by multiple factors, including solution temperature, pH, osmolarity, hydrostatic pressure, caffeine ingestion, and circadian timing. Warm vinegar elicited a faster and more consistent SSW response compared to other tested conditions, highlighting its use in experimental settings. No difference in SSW was observed between room-temperature vinegar and EMLA after 10 min, supporting its potential for clinical application.

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