Decreased alertness due to sleep loss increases pain sensitivity in mice

Alexandre, C; Latrémolière, Alban; Ferreira, Ashley N.; Miracca, Giulia; Yamamoto, Masahiro; Scammell, Thomas E.; Woolf, Clifford J.

doi:10.1038/nm.4329

Cited by 139 publications

(125 citation statements)

References 67 publications

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“…Alertness is known to affect many functions, such as performance, psychological and physiological well‐being, caloric intake, and pain sensitivity . Displaying optimal alertness is thus beneficial, and many studies have attempted to improve alertness using monochromatic or polychromatic light (for review see,).…”

Section: Introductionmentioning

confidence: 99%

“…13 Alertness is known to affect many functions, such as performance, psychological and physiological well-being, caloric intake, and pain sensitivity. [14][15][16][17] Displaying optimal alertness is thus beneficial, and many studies have attempted to improve alertness using monochromatic or polychromatic light (for review see, 18,19 ). Exposure to light improves alertness during nighttime, when melatonin concentrations are usually high and CBT decreases.…”

Section: Introductionmentioning

confidence: 99%

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Daytime melatonin and light independently affect human alertness and body temperature

Lok

Koningsveld

Gordijn

et al. 2019

Journal of Pineal Research

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Light significantly improves alertness during the night (Cajochen, Sleep Med Rev, 11, 2007 and 453; Ruger et al., AJP Regul Integr Comp Physiol, 290, 2005 and R1413), but results are less conclusive at daytime (Lok et al., J Biol Rhythms, 33, 2018 and 589). Melatonin and core body temperature levels at those times of day may contribute to differences in alerting effects of light. In this experiment, the combined effect of daytime exogenous melatonin administration and light intensity on alertness, body temperature, and skin temperature was studied. The goal was to assess whether (a) alerting effects of light are melatonin dependent, (b) soporific effects of melatonin are mediated via the thermoregulatory system, and (c) light can improve alertness after melatonin‐induced sleepiness during daytime. 10 subjects (5 females, 5 males) received melatonin (5 mg) in dim (10 lux) and, on a separate occasion, in bright polychromatic white light (2000 lux). In addition, they received placebo both under dim and bright light conditions. Subjects participated in all four conditions in a balanced order, yielding a balanced within‐subject design, lasting from noon to 04:00 pm. Alertness and performance were assessed half hourly, while body temperature and skin temperature were measured continuously. Saliva samples to detect melatonin concentrations were collected half hourly. Melatonin administration increased melatonin concentrations in all subjects. Subjective sleepiness and distal skin temperature increased after melatonin ingestion. Bright light exposure after melatonin administration did not change subjective alertness scores, but body temperature and proximal skin temperature increased, while distal skin temperature decreased. Light exposure did not significantly affect these parameters in the placebo condition. These results indicate that (a) exogenous melatonin administration during daytime increases subjective sleepiness, confirming a role for melatonin in sleepiness regulation, (b) bright light exposure after melatonin ingestion significantly affected thermoregulatory parameters without altering subjective sleepiness, therefore temperature changes seem nonessential for melatonin‐induced sleepiness, (c) subjective sleepiness was increased by melatonin ingestion, but bright light administration was not able to improve melatonin‐induced sleepiness feelings nor performance. Other (physiological) factors may therefore contribute to differences in alerting effects of light during daytime and nighttime.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Daytime melatonin and light independently affect human alertness and body temperature

Lok

Koningsveld

Gordijn

et al. 2019

Journal of Pineal Research

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“…While the endocrine system, including proopiomelanocortins and endorphins, is most often linked to pain syndromes, there exists a role for most hormones in acute and chronic pain (Chen, Zhang, & Wang, ; Csaba, ). For instance, a recent study on the role of sleep in naïve noxious pain showed that sleep deprivation exacerbates sensitivity to mechanical and thermal stimuli, an effect that is dependent on prostanoids produced by cyclooxygenases (Alexandre et al, ). There is also a prominent role for hormones in the circadian entrainment of peripheral clocks, particularly glucocorticoids: dexamethasone treatment induces circadian gene expression in cultured rat fibroblasts but not SCN neurons (Balsalobre et al, ).…”

Section: Circadian Control Of Inflammatory Mediatorsmentioning

confidence: 99%

Circadian control of pain and neuroinflammation

Segal

Tresidder

Bhatt

et al. 2017

J of Neuroscience Research

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The importance of a neuroinflammatory response to the development and maintenance of inflammatory and neuropathic pain have been highlighted in recent years. Inflammatory cells contributing to this response include circulating immune cells such as monocytes, T and B lymphocytes, and neutrophils, as well as microglia in the central nervous system. Pain signals are transmitted via sensory neurons in the peripheral nervous system, which express various receptors and channels that respond to mediators secreted from these inflammatory cells. Chronobiological rhythms, which include the 24-hr circadian cycle, have recently been shown to regulate both nervous and immune cell activity and function. This review examines the current literature on chronobiological control of neuroinflammatory processes, with a focus on inflammatory and neuropathic pain states. While the majority of this work has stemmed from observational studies in humans, recent advances in using animal models have highlighted distinct mechanisms underlying these interactions. Better understanding interactions between the circadian and neuroimmune systems can help guide the development of new treatments and provide improved care for patients suffering from acute and chronic pain.

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“…A high level of alertness is defined as a state of high sensitivity to incoming stimuli 4 . It is known to affect many psychological and physiological functions, such as performance, caloric intake and pain sensitivity [5][6][7][8] . Polychromatic white light has been shown to significantly improve alertness during the evening and night 3 .…”

Section: Introductionmentioning

confidence: 99%

Light effects on circadian and homeostatic regulation: alertness increases independent of time awake

Lok

Woelders

Koningsveld

et al. 2020

Preprint

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Light induced improvements in alertness are more prominent during night-time than during the day, indicating circadian regulation or wake duration related dependence. Relative contributions of both factors can be quantified using a forced desynchrony (FD) designs. Here we investigate alerting effects of light in a novel 4x18 hours FD protocol (5h sleep, 13h wake) under dim (6 mlux) and bright light (1159 mlux) conditions. Hourly saliva samples (melatonin and cortisol assessment) and 2-hourly test-sessions were used to assess effects of bright light on subjective and objective alertness (electroencephalography and performance). Results reveal (1) stable free-running cortisol rhythms with uniform phase progression under both light conditions, indicating that FD designs can be conducted under high intensity lighting, (2) subjective alerting effects of light depend on elapsed time awake, while (3) light consistently improves objective alertness independent of time awake. Three dimensional graphs reflecting light induced alertness improvements depending on wake duration related variation and circadian clock phase suggest that performance is improved during daytime, while subjective alertness remains unchanged. This suggests that light during office hours might be beneficial for performance, even though this may not be perceived as such.

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Decreased alertness due to sleep loss increases pain sensitivity in mice

Cited by 139 publications

References 67 publications

Daytime melatonin and light independently affect human alertness and body temperature

Daytime melatonin and light independently affect human alertness and body temperature

Circadian control of pain and neuroinflammation

Light effects on circadian and homeostatic regulation: alertness increases independent of time awake

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