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One night of total sleep deprivation promotes a state of generalized hyperalgesia: A surrogate pain model to study the relationship of insomnia and pain
Abstract
Sleep disturbances are highly prevalent in chronic pain patients. Understanding their relationship has become an important research topic since poor sleep and pain are assumed to closely interact. To date, human experimental studies exploring the impact of sleep disruption/deprivation on pain perception have yielded conflicting results. This inconsistency may be due to the large heterogeneity of study populations and study protocols previously used. In addition, none of the previous studies investigated the entire spectrum of nociceptive modalities. To address these shortcomings, a standardized comprehensive quantitative sensory protocol was used in order to compare the somatosensory profile of 14 healthy subjects (6 female, 8 male, 23.5 ± 4.1 year; mean ± SD) after a night of total sleep deprivation (TSD) and a night of habitual sleep in a cross-over design. One night of TSD significantly increased the level of sleepiness (P<0.001) and resulted in higher scores of the State Anxiety Inventory (P<0.01). In addition to previously reported hyperalgesia to heat (P<0.05) and blunt pressure (P<0.05), study participants developed hyperalgesia to cold (P<0.01) and increased mechanical pain sensitivity to pinprick stimuli (P<0.05) but no changes in temporal summation. Paradoxical heat sensations or dynamic mechanical allodynia were absent. TSD selectively modulated nociception, since detection thresholds of non-nociceptive modalities remained unchanged. Our findings show that a single night of TSD is able to induce generalized hyperalgesia and to increase State Anxiety scores. In the future, TSD may serve as a translational pain model to elucidate the pathomechanisms underlying the hyperalgesic effect of sleep disturbances.
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“Exerciseinduced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic (Tantimonaco et al., 2014;Fuss et al., 2015), anti-nociceptive (Galdino et al., 2014) and neuroprotective (Hill et al., 2010a) properties of exercise, which are all responses that instead are affected in a negative direction by sleep loss (e.g.Roy-Byrne et al., 1986;Schuh-Hofer et al., 2013;”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Schuh-Hofer et al., 2013
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The Role of Sleep in Learning Placebo Effects
Chouchou, F., Dang‐Vu, T. T., Rainville, P., & Lavigne, G. J. (2018) · International review of neurobiology · doi:10.1016/bs.irn.2018.07.013 · Cited by 11
Day/night melatonin content in cerebral palsy
Santos, J. S., Giacheti, C. M., Dornelas, L. M. C. D. S. [., da Silva, N. C., de Souza, A. L. D. M., Campos, L. M. G., & Pinato, L. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.08.045 · Cited by 10
“It is known that pain interferes with sleep and there is evidence that this may be a bidirectional relationship and should be taken into account when discussing sleep problems [43] however, in the present study, there was no report by parents of presence of pain in the sample.”
Sleep as a Therapeutic Target for Pain Management
Hu, L., & Wang, E. J. (2023) · Current Pain and Headache Reports · doi:10.1007/s11916-023-01115-4 · Cited by 11
“showed that even just one night of sleep deprivation increased hyperalgesia to cold, pinprick, blunt pressure, and heat stimuli in healthy volunteers [22].”
BackgroundFalling, C., Stebbings, S. M., Baxter, D. G., Siegel, C. A., Gearry, R. B., Nijs, J., & Mani, R. (2020) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2020-0109 · Cited by 9
van den Berg, B., Hijma, H. J., Koopmans, I. W., Doll, R. J., Zuiker, R. G. J. A., Groeneveld, G. J., & Buitenweg, J. R. (2022) · Experimental Brain Research · doi:10.1007/s00221-021-06284-5 · Cited by 10
Factores predictores de la calidad del sueño en pacientes con migraña crónica
Garrigós-Pedrón, M., Segura‐Ortí, E., Gracia-Naya, M., & Touche, R. L. (2019) · Neurología · doi:10.1016/j.nrl.2018.11.004 · Cited by 10
Yin, X., Chen, B.-R., Ye, X.-C., & Wang, Y. (2024) · Neuroscience Bulletin · doi:10.1007/s12264-024-01281-4 · Cited by 8
“Research has shown that one night of sleep deprivation in healthy volunteers results in a decrease in pain threshold [31], and 6 h of sleep deprivation leads to hyperalgesia in mice [7].”
Psychophysical changes after total sleep deprivation and experimental muscle pain
Hertel, E., Sathiyalingam, E., Pilgaard, L., Brommann, S. J., Giordano, R., & Petersen, K. K. (2024) · Journal of Sleep Research · doi:10.1111/jsr.14329 · Cited by 10
“Similarly, discrepancies exist regarding changes in TSP following experimental sleep provocations ranging from facilitation (Hertel et al., 2023; Staffe et al., 2019) to no changes (Schuh-Hofer et al., 2013).”
Nelson, M. J., Yu, D. A., Ha, A. V. H., Wakefield, M. R., & Fang, Y. (2025) · Clocks & Sleep · doi:10.3390/clockssleep7030029 · Cited by 10
“However, the effect that poor sleep quality has on pain perception is larger than the effect pain has on decreasing sleep quality [92,93], and just one night of sleep deprivation is enough to aid in the development of hyperalgesia [94].”
Looveren, E. V., Meeus, M., Cagnie, B. J., Ickmans, K., Bilterys, T., Malfliet, A., Goubert, D., Nijs, J., Danneels, L. A., Moens, M., et al. (2022) · Physical Therapy · doi:10.1093/ptj/pzac075 · Cited by 9
Nishimori, H., Iida, T., Kamiyama, H., Honda, M., Masuda, M., Laat, A. D., & Komiyama, O. (2018) · Journal of Prosthodontic Research · doi:10.1016/j.jpor.2018.11.005 · Cited by 8
Sleep disorders in acute and chronic pain
Poluektov, M. G., & Golovatyuk, A. O. (2021) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2021-3-125-130 · Cited by 8
Noziplastischer Schmerz in Forschung und Praxis
Schmidt, H., & Blechschmidt, V. (2023) · Der Schmerz · doi:10.1007/s00482-023-00734-5 · Cited by 9
Insomnia and cognitive behavioral therapy for chronic back pain
Parfenova, E. V. (2020) · Neurology neuropsychiatry Psychosomatics · doi:10.14412/2074-2711-2020-4-119-124 · Cited by 8
Poor Sleep Predicts Increased Pain Perception Among Adults With Mild Cognitive Impairment
Bowen, M. E., Ji, X., & Griffioen, M. A. (2021) · Nursing Research · doi:10.1097/nnr.0000000000000506 · Cited by 8
“For example, pain interference is associated with increased analgesic use (Shade et al., 2019), depressive symptoms (Wang et al., 2018), higher mortality rates (Smith et al., 2018), and increased rates of dementia among community-dwelling older adults (Letzen et al., 2020).”
BackgroundChronic sleep deficiency and its impact on pain perception in healthy females
Rouhi, S., Egorova, N., & Jordan, A. S. (2024) · Journal of Sleep Research · doi:10.1111/jsr.14284 · Cited by 7
Sex and Sleep Quality Effects on the Relationship Between Sleep Disruption and Pain Sensitivity
Joensen, E. D. R., Frederiksen, L., Frederiksen, S. V., Valeur, E. S., Giordano, R., Hertel, E., & Petersen, K. K. (2025) · European Journal of Pain · doi:10.1002/ejp.70023 · Cited by 9
“Several studies have found an association between experimental sleep disturbance and increased pressure pain sensitivity in healthy individuals (Faraut et al. 2015; Schuh-Hofer et al. 2013; Simpson et al. 2018; Staffe et al. 2019).”
The Role of Polysomnography in Identifying Sleep Disorders in Children with Migraine
Nita, S. A., Teleanu, R. I., & Bajenaru, O. A. (2020) · Journal of Medicine and Life · doi:10.25122/jml-2020-0025 · Cited by 7
“Also, some studies enquire about the role of sleep deprivation in modulating pain and hyperalgesia [1].”
BackgroundCluster Headache Pathophysiology—A Disorder of Network Excitability?
Pohl, H., Sándor, P. S., Michels, L., & Gantenbein, A. R. (2021) · Clinical and Translational Neuroscience · doi:10.3390/ctn5020016 · Cited by 7
The Sleep-Reward-Pain Pathway Model: an Integrative Review
Reid, M. J., Climent‐Sanz, C., & Finan, P. H. (2022) · Current Sleep Medicine Reports · doi:10.1007/s40675-022-00232-7 · Cited by 7
DiMarco, L. A., Ramger, B., Howell, G. P., Serrani, A. M., Givens, D. L., Rhon, D. I., & Cook, C. E. (2018) · Pain Practice · doi:10.1111/papr.12728 · Cited by 7
Martínez-Magaña, C. J., Muñoz-Castillo, P. A., & Murbartián, J. (2024) · Brain Research · doi:10.1016/j.brainres.2024.148915 · Cited by 6
Olia, K., Goldstein, M. R., Engert, L. C., Besedovsky, L., Dang, R., Bertisch, S. M., Sethna, N. F., & Haack, M. (2025) · European Journal of Pain · doi:10.1002/ejp.4789 · Cited by 7
“…or sleep disturbance) (Hertel, McPhee, and Petersen 2023; Hijma et al. 2023; Kundermann et al. 2004; Matre et al. 2016; Onen et al. 2001; Roehrs et al. 2006; Schuh-Hofer et al. 2013; Simpson et al. 2018; Staffe et al. 2019; Tiede et al. 2010), but the modulation by sex has been largely neglected.”
Woldeamanuel, Y. W., Blayney, D. W., Jo, B., Fisher, S. E., Benedict, C., Oakley-Girvan, I. A., Kesler, S. R., & Palesh, O. G. (2021) · Cancer · doi:10.1002/cncr.33844 · Cited by 6
A Model to guide force-based manipulation research and practice
Loghmani, M. T., Keter, D. L., Bove, G. M., Winkelstein, B. A., Bulea, T. C., Olausson, H., Pathak, M. N., Powell, R., & Cook, C. E. (2025) · PLoS ONE · doi:10.1371/journal.pone.0331606 · Cited by 5
“…stress, fear, anxiety) [15–21] Treatment expectations [22–28] Physical Status (e.g., comorbid conditions, sleep status, fatigue, activity level) [15,29–39] Animal: Fear and empathy Previous experience/expectations [40,41] In vitro: Prior tissue use (previous load) Tissue storage conditions [42–45]…”
Alves, A. A., Antonio, G. L. N., Noronha, M. A. D., & Selistre, L. F. A. (2024) · Musculoskeletal Science and Practice · doi:10.1016/j.msksp.2024.103183 · Cited by 5
Metadata
- Authors
- Schuh-Hofer, S., Wodarski, R., Pfau, D. B., Caspani, O., Magerl, W., Kennedy, J. D., & Treede, R.-D.
- Affiliations
- Eli Lilly (United States) (US)
- Heidelberg University (DE)
- Venue
- Pain
- Published
- 2013-09
- Volume
- 154
- Issue
- 9
- Pages
- 1613-1621
- ISSN
- 0304-3959 (ISSN-L)
- OpenAlex
- W2094084202
- Cited by
- 296
- References
- 109
- Citations by year
- 2026: 17 · 2025: 26 · 2024: 18 · 2023: 27 · 2022: 27 · 2021: 22 · 2020: 21 · 2019: 23 · 2018: 18 · 2017: 20 · 2016: 23 · 2015: 30 · 2014: 19 · 2013: 5
- FWCI
- 17.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Commission
- Innovative Medicines Initiative
- Topics
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- total sleep deprivation, hyperalgesia, insomnia, pain perception, nociception, quantitative sensory testing, mechanical allodynia, state anxiety, sleepiness
- MeSH terms
- Adult, Anxiety, Female, Humans, Hyperalgesia, Male, Pain, Pain Measurement, Physical Stimulation, Sleep Deprivation, Pain Threshold, Cross-Over Studies, Young Adult, Pain Perception
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