Daguet, I. | bioRxiv Science

bioRxiv2024

Circadian rhythmicity and photobiological mechanisms of light sensitivity and discomfort glare in humans

Discomfort glare is a common visual sensation, which is generally reported when being exposed to a brighter lit environment. In certain clinical conditions, this sensation is abnormally amplified, and is commonly named photophobia. Despite the frequent appearance of this sensation in everyday life or in pathological conditions, the underlying mechanisms remain poorly understood. We show here, in highly controlled laboratory constant routine conditions, that light-induced discomfort glare is rhythmic over the 24-hour day. We reveal a strong circadian drive, with a sinusoidal rhythmicity, with maximal discomfort glare in the middle of the night and minimal in the afternoon. We also find a modest sleep-related homeostatic drive of visual discomfort, with a linear increase in discomfort glare over 34 hours of prolonged wakefulness. Our study reveals that discomfort glare is primarily driven by the ipRGC pathway, and that mid and/or long wavelengths cones are involved as well. The 6.5-hour phase lag between the rhythms of photoreceptors sensitivity, assessed through pupillary light reflex, and of glare discomfort, suggests two independent underlying mechanisms. In conclusion, our findings highlight the need to take time-of-day and biological rhythmicity into account in the evaluation of light-induced discomfort glare. Apprehending these mechanisms may help understand photophobia in clinical populations, such as in migraine patients, and should be taken into account to optimize light quality at home and at the workplace, both for day and night work.

neuroscience↗

bioRxiv2020

Evidence that pain sensitivity is rhythmic in humans, mainly driven by the endogenous circadian system and little by sleep

Pain intensity has been reported to fluctuate during the day in some experimental and clinical conditions, but the mechanisms underlying these fluctuations are unknown. Although the circadian timing system is known to regulate a wide range of physiological functions, its implication in pain regulation is unknown. We show here, using highly controlled laboratory constant routine conditions, that pain sensitivity is rhythmic over the 24-hours and strongly controlled by the endogenous circadian timing system. We find that pain sensitivity follows a sinusoidal circadian rhythmicity, with a maximum in the middle of the night and a minimum in the afternoon. We also find a weak homeostatic control of pain sensitivity, with a linear increase over the 34 hours of prolonged wakefulness, which parallels that of sleep pressure. Using mathematical modelling, we describe that the circadian system accounts for 80% of the full magnitude of pain sensitivity over the 24 hours, and that sleep-related processes account for only 20%. This result reveals that nocturnal analgesia is predominantly induced by the circadian system and has been wrongly attributed only to sleep. Our findings highlight the need to consider the time of day in pain assessment, and suggest that personalized circadian medicine may be a promising approach to pain management. Significance statementWe discovered that sensitivity to pain is rhythmic in healthy humans, that sensitivity is maximal at night and minimal in the afternoon. Contrarily to the current thinking that sleep is the best painkiller, we find that the 24-h rhythmicity of sensitivity to pain is mainly controlled by a biological circadian clock in our body, and very little by our sleep. Our article reveals the neurobiological mechanisms involved in driving the rhythmicity of pain perception in humans, with the main time-piece located in the brain (the suprachiasmatic nuclei in the hypothalamus). Our findings challenge the current vision of pain physiology, and reveal the need to consider time-of-day and internal biological time for pain evaluation and pain management.

neuroscience↗