Offset Analgesia in Neuropathic Pain Patients and Effect of Treatment with Morphine and Ketamine

Abstract

Background Offset analgesia, in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation, has not been described previously in patients with chronic pain. Methods Offset analgesia responses in 10 patients with neuropathic pain (in both legs) were compared with 10 matched healthy controls and volunteers from a convenience sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by the reduction in electronic pain score upon the 1°C decrease in noxious heat stimulus relative to the peak pain score where pain was administered at the volar side of the arm. Results Offset analgesia was present in healthy volunteers irrespective of age and sex (pain score decrease = 97 ± 1% [mean ± SEM]). In contrast, a reduced or absent offset analgesia response was observed in patients with neuropathic pain (pain score decrease = 56 ± 9% vs. controls 98 ± 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo had no effect on offset analgesia in patients, despite sharp reductions in spontaneous pain scores. Conclusions These data indicate that offset analgesia is fully developed at the age of 6 yr and does not undergo additional maturation. The reduced or absent responses observed in patients with chronic neuropathic pain indicate the inability to modulate changes in pain stimulation, with perseverance of pain perception in situations in which healthy subjects display signs of strong analgesia. Both central and peripheral sites may be involved in the altered offset analgesia responses in these patients.