Cold stimulation applied concurrently with high-frequency electrical stimulation does not attenuate the development of pinprick hypersensitivity in humans

Diffuse noxious inhibitory controls (DNIC) reduce spinal nociceptive processing in animal models, and the human analogue, conditioned pain modulation (CPM), is thought to engage descending inhibitory pathways. A recent translational study reported that neither cuff-induced DNIC in animals nor cuff-induced CPM in humans interferes with high-frequency electrical stimulation (HFS)–induced spinal sensitization in animals or secondary pinprick hypersensitivity in humans. In contrast, another human study, using cold-water immersion to induce CPM, observed a substantial reduction in low-frequency stimulation (LFS)-induced secondary pinprick hypersensitivity. Here, we tested whether cold-water immersion applied concurrently with HFS reduces HFS-evoked pain and attenuates the subsequent development of secondary pinprick hypersensitivity. In a preregistered crossover study, healthy participants (N = 30) received HFS on the forearm during immersion of the contralateral hand in either 4°C water (experimental condition) or room-temperature water (control condition). Pressure pain thresholds (PPTs), HFS-evoked pain ratings, and the magnitude and spatial extent of secondary pinprick hypersensitivity were assessed. Cold-water immersion, but not room temperature water, significantly increased PPTs, confirming the CPM effect. However, neither HFS-evoked pain nor the intensity or spatial extent of HFS-induced secondary pinprick hypersensitivity differed between conditions. Under the present experimental conditions, recruitment of pain-inhibitory mechanisms by cold-water immersion was insufficient to meaningfully alter the development of HFS-induced secondary pinprick hypersensitivity.