Time-dependent microvascular and analgesic responses to cold compression in healthy adults: identifying the optimal...

Because the ankle-foot complex is a frequent target of cryotherapy in sports medicine, establishing location-specific duration guidance has practical clinical relevance. Thus, the aim of this study was to determine how ankle-applied cold compression duration shapes microvascular perfusion at the foot dorsum, cold-induced vasodilation (CIVD), post-cooling hyperaemia, and analgesia, and to identify a pragmatic exposure window that maximizes vasoconstriction and pressure-pain threshold (PPT) while limiting CIVD/hyperaemia in healthy adults.

Prospective, randomized, controlled, parallel-group trial with a repeated-measures duration factor using an ankle-foot cuff. Sixty healthy volunteers were allocated 1:1 to Active cold compression (ACC; ~3 °C, 5-75 mmHg) or sham (shamCC; 20 °C, ~ 15 mmHg). Each participant completed four sessions (5, 10, 15, 20 min), order randomized with ≥ 7-day washouts. Primary outcomes were laser-Doppler perfusion indices at the foot dorsum; secondary outcome was PPT by algometry.

Minimum perfusion (nadir) showed a strong duration effect and a condition×group interaction; ACC achieved lower perfusion than sham at 5, 10, 15, and 20 min (all p < 0.001), with progressive nadir reductions from 10→20 min in ACC (p ≤ 0.018). Time-to-nadir decreased with longer exposures (main effect p < 0.001). CIVD at the foot increased with duration and was higher in ACC at 15 min (p = 0.004) and 20 min (p < 0.001). Post-cooling hyperaemia (AUC) showed large effects for duration and group; between-group differences favored ACC at 0-15 min for all durations (all p ≤ 0.001), with stepwise increases from 5→20 min in ACC (all p < 0.001). Post-peak perfusion was greater with ACC at 10-20 min (all p < 0.001). At post-intervention PPT was higher with ACC at 5 min (p = 0.005), 10 min (p < 0.001), 15 min (p < 0.001), and 20 min (p < 0.001). Within ACC, 10, 15, and 20 min produced similar (and greater) PPT improvements, each exceeding 5 min (all p ≤ 0.001).

ACC elicited dose-dependent vasoconstriction and robust hypoalgesia, with PPT improvements plateauing by 10 min. Because CIVD and post-cooling hyperaemia escalated at ≥ 15 min, a 10-minute ACC bout best balanced analgesia with vascular control, limiting disproportionate rebound perfusion and preserving a physiological equilibrium between vasoconstriction and vascular reopening; extending to 15 min can be reserved for cases needing marginal additional relief.

ISRCTN90040217; date: 25/05/2023.