Overnight fasting reduces the development of mechanical hypersensitivity induced by cutaneous high-frequency electrical stimulation in humans

Preclinical studies suggest that fasting may attenuate spontaneous pain and pain-related behaviors, such as licking and paw withdrawal, during inflammation in animals; however, evidence of the analgesic effects of fasting in patients suffering from chronic pain remains inconclusive. In two studies, we investigated the potentially protective effects of fasting on the development of mechanical hypersensitivity in healthy human volunteers following experimentally induced sensitization of nociceptive fibers through painful cutaneous electrical stimulation. In the first experiment (N = 33), participants underwent the painful electrical stimulation protocol twice: once after a 12-hour fast and once after consuming a standard breakfast. In a follow-up experiment (N = 52), participants were randomized to receive either the painful electrical stimulation protocol after a 16-hour fast or after their usual morning meal. In both experiments, we assessed the intensity, unpleasantness, and spatial extent of secondary mechanical hypersensitivity, as well as emotional state and hunger levels. Fasting increased hunger and negative affect in both studies. In Experiment 2, but not in Experiment 1, participants in the fasted condition reported significantly less mechanical hypersensitivity compared to the breakfast condition. In both experiments, fasting did not reduce the pain intensity reported during the painful electrical stimulation. These findings provide behavioral evidence that a 16-hour fast may reduce the development of mechanical hypersensitivity. These results in humans align with preclinical evidence showing that fasting affects mechanical hypersensitivity, without necessarily affecting the perceived intensity of acute painful stimuli. Our findings suggest that metabolic state may modulate mechanical hypersensitivity in humans.