A Scoping Review of the Diurnal Variation in the Intensity of Neuropathic Pain

Abstract

Background: Recent studies have suggested that neuropathic pain exhibits a daily diurnal pattern, with peak levels usually occurring in the late afternoon to evening and the trough in the morning hours, although literature on this topic has been sparse. This scoping review examines current evidence on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain.

Methods: A literature search was conducted in major medical databases for relevant articles on the chronobiology of neuropathic pain both in animal models and in humans with neuropathic pain. Data extracted included details of specific animal models or specific neuropathic pain conditions in humans, methods and timing of assessing pain severity, and specific findings of diurnal variation in pain intensity or its surrogate markers.

Results: Thirteen animal and eight human studies published between 1976 and 2020 were included in the analysis. Seven of the 13 animal studies reported specific diurnal variation in pain intensity, with five of the seven studies reporting a trend toward increased sensitivity to mechanical allodynia or thermal hyperalgesia in the late light to dark phase. All eight studies in human subjects reported a diurnal variation in the intensity of neuropathic pain, where there was an increase in pain intensity through the day with peaks in the late evening and early night hours.

Conclusions: Studies included in this review demonstrated a diurnal variation in the pattern of neuropathic pain that is distinct from the pattern for nociceptive pain. These findings have implications for potential therapeutic strategies for neuropathic pain.

Keywords: Chronic Pain; Chronobiology; Diurnal Variation; Neuropathic Pain; Sleep.