2026/07/13 by Emanuel N. van den Broeke, Elise Ercken, Linde Maes +2
Medicine · Neuroscience · #Pain Mechanisms and Treatments #Pain Management and Treatment #Transcranial Magnetic Stimulation Studies
paper · doi:10.1152/jn.00075.2026
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.