The influence of rapid eye movement sleep deprivation on nociceptive transmission and the duration of facial allodynia in rats: A behavioral and Fos immunohistochemical study

Background: Disrupted sleep is associated with a reciprocal influence on headaches and is one of the contributing factors in the process of chronicity. The goal of the present study was to investigate the influence of sleep on headaches using animal rapid eye movement (REM) sleep deprivation and supradural capsaicin infusion models. Method: Sprague-Dawley rats underwent REM sleep deprivation (REMSD) for 96 h. The sensory threshold to mechanical stimuli, assessed by the von Frey monofilament test, was measured during the REMSD period. Additionally, the Fos protein expression level was measured in the trigeminocervical complex, periaqueductal gray, and hypothalamus. Following supradural infusion of capsaicin, we evaluated the duration of facial allodynia for 28 days after REMSD. Results: After REMSD, the sensory threshold to mechanical stimuli was significantly decreased (p < 0.01) and Fos-positivity in the posterior (p = 0.010) and dorsomedial hypothalamus (p = 0.024), ventrolateral periaqueductal gray (p = 0.016), and superficial layer of the trigeminocervical complex (p = 0.019) were significantly increased. The duration of facial allodynia induced by supradural capsaicin infusion was significantly longer in the REM sleep deprivation and capsaicin infusion group (Day 10 PSD vs. Day 25 PSD). Conclusion: The present study demonstrates that REM sleep deprivation increased nociceptive transmission from trigeminal nerve endings. Furthermore, it suggests that sleep deprivation may contribute to the chronicity of facial allodynia.