This study assessed a newly developed cuff pressure algometry during discrete leg skin/muscle sensitization and anesthesia. Experimental setup consisted of a pneumatic tourniquet cuff, a computer-controlled air compressor, and an electronic visual analog scale (VAS). The first experiment assessed cuff algometry before and after selective anesthesia of the skin and the muscle under the cuff. The second experiment assessed cuff algometry before and during skin and muscle sensitization with capsaicin cream and injection of capsaicin. Pressure-pain detection threshold, pressure equivalent to the pain intensity of 2 on the VAS (PVAS2), pressure-pain tolerance threshold, and pressure-pain stimulus-response (SR) function were evaluated. Local anesthesia of the muscle increased the pain thresholds significantly and shifted the average SR function to the right indicating desensitization, whereas cutaneous anesthesia did not affect the pressure thresholds and increased the slope of the SR function. Capsaicin cream did not affect pressure-pain tolerance threshold, whereas PVAS2 and the slope of the SR function were significantly decreased. Intramuscular capsaicin injection decreased the pain thresholds and did not affect the slope of the SR function. Both interventions shifted the SR function to the left. The cuff algometry reliably assessed the pressure-pain SR function during muscle sensitization/desensitization and might supplement conventional pressure algometry for standardized pressure-pain function assessment.