Deficits in temporal pain inhibition are associated with greater pain and functional impairment in osteoarthritis

Offset analgesia reflects time-dependent, central nervous system pain inhibition and refers to a dramatic drop in pain intensity after an offset of noxious stimulus intensity. Neuropathic and nociplastic pain conditions with strong central nervous system pathophysiologic mechanisms show deficits in offset analgesia. Whether offset analgesia is altered in more peripherally driven chronic nociceptive pain was unknown. Therefore, the primary goal of the current study was to determine whether chronic nociceptive pain is associated with changes in offset analgesia. We measured offset analgesia and sensory function using quantitative sensory tests, patient-reported pain and function, and walking and stair climbing performance using standardized tasks in knee osteoarthritis patients with equivalent joint degeneration but Moderate-to-Severe (n = 36) or Mild pain intensity (n = 36) and Pain-free controls without knee osteoarthritis (n = 30) matching for age, gender, and body mass index. Offset analgesia was significantly reduced in knee osteoarthritis groups compared with the Pain-free controls, with deficits occurring at both the nonpainful forearm and painful knee and in both genders. Greater deficits in offset analgesia were associated with more impairment in walking and stair climbing. Onset hyperalgesia, a novel measure of time-dependent pain facilitation, was reduced in women with Mild knee pain but not in men. These results suggest that deficits in temporal pain inhibition and gender-specific changes in temporal pain facilitation may contribute to pain and functional impairment in knee osteoarthritis, supporting further study of central pain modulation as a clinically relevant mechanism of chronic nociceptive pain.