Perception of first and second pain during offset analgesia

Offset analgesia (OA) is a disproportionate reduction in pain perception following a small decrease in noxious stimulation. However, the underlying mechanisms remain a matter of debate. At the peripheral level, specific contributions of A-δ nociceptors have been proposed, although some studies have reported conflicting results. This study aimed to investigate (A-δ vs. C-fiber) fiber contributions to OA by psychophysical assessment of first and second pain sensations in healthy individuals. Thirty-two pain-free participants underwent a randomized within-subject study with two distinct goals: (1) testing the concept of first and second pain to brief heat pulses; (2) investigating brief heat pulses applied during the analgesic phase of OA. Response times (RT), the perception of double sensations and fiber-specific pain descriptors were assessed to detect alterations suggesting predominant A-δ or C-fiber involvement. No significant differences were found between offset and control (constant) trials for the first or second pain reporting or the fiber-specific pain descriptors (p > 0.05). Nevertheless, a significant main effect of trial type and stimulus timing on RTs was observed (p = 0.03, η 2 p​  = 0.02). Response times to noxious stimuli was delayed following prolonged stimulation in both offset and control trials (p < 0.05). The findings suggest that A-δ and C-fiber response characteristics were unaffected during the OA paradigm; however, higher stimulation intensities or prolonged pain induced a notably longer RT. This may indicate that specific peripheral nerve fibers play a negligible role in OA, however future studies should complement psychophysical assessment with more objective procedures to conclusively rule out peripheral contributions.