Analgesics and anti-inflammatory drugs represent the largest segment of over-the-counter (OTC) medicines. This observational study involved 247 patients treated for pain in outpatient physiotherapy. Using Transcutaneous Electrical Nerve Stimulation (TENS) sensitivity threshold was measured together with subjective sensation (hedonic rating), investigating the impact of OTC analgesic intake on sensory sensitivity and subjective perception. Additionally, the influence of sex, age, height, and body mass index (BMI) on sensitivity threshold was assessed. Sensory threshold was significantly affected by age (B = 0.04, % variance = 5.84, p < 0.001), BMI (B = 0.22, % variance = 5.71, p = 0.001), and use of OTC analgesics up to 8 h beforehand (B = 0.83, % variance = 3.87, p = 0.001). The OTC drugs with the strongest effect on sensory threshold were Ibuprofen 400 mg (B = 0.91, % variance = 3.01, p = 0.003). Compared to individuals who did not use pain medication and predominantly experienced the stimulus as pleasant (53.37%), those who had taken analgesics more frequently reported a neutral perception of TENS stimulation (65.22%) and exhibited higher sensory thresholds. These findings suggest that OTC analgesics may alter neurosensory responses, highlighting a potential interaction not previously considered in standard pharmacological information. Further double-blind controlled trials are warranted to validate these observations and elucidate underlying mechanisms.