Cited by 150Pain Mechanisms and TreatmentsSleep and Work-Related FatiguePain Management and Treatment

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Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants

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Staffe, Alexander Torp, Bech, Mathias Winther, Clemmensen, Sara Louise Kjær, Nielsen, Henriette Tranberg, Larsen, Dennis Boye, Petersen, Kristian Kjær·2019·PLoS ONE

DOI 10.1371/journal.pone.0225849PMC PMC6892491

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Abstract

Chronic pain patients often suffer from insomnia or impaired sleep which has been associated with increased pain sensitivity, but a limited amount of studies have investigated the effects of total sleep deprivation on central pain mechanisms. Therefore, the aim of this study was to determine the effects of total sleep deprivation on temporal summation, conditioned pain modulation, thermal and pressure pain sensitivity in healthy participants. Twenty-four healthy participants took part in this two-session trial. The measurements were conducted after a night of habitual sleep (baseline) and following 24 hours of total sleep deprivation. Detection thresholds for cold and warmth and pain thresholds for cold and heat were assessed. Cuff induced pressure pain detection and tolerance thresholds, temporal summation and conditioned pain modulation were assessed with user-independent, computer-controlled cuff algometry. Conditioned pain modulation was significantly impaired, temporal summation was significantly facilitated and pain sensitivity to pressure and cold pain were significantly increased at follow-up compared with baseline. In conclusion, this study found that one night of total sleep deprivation impaired descending pain pathways, facilitated spinal excitability and sensitized peripheral pathways to cold and pressure pain. Future studies are encouraged to investigate if sleep therapy might normalize pain sensitivity in sleep-deprived chronic pain patients.

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MethodInfluential
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Background
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Background
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Background
Modulation of Exercise-Induced Hypoalgesia Following an Exercise Intervention in Healthy Subjects
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Background
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Obstructive sleep apnea treatment improves temporomandibular disorder pain
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“However, this limitation does not undermine the present results as it has been shown that short-lasting sleep deprivation is associated with increased pain sensitivity [43] and that pain-related TMDs are often self-limiting when the identified source of pain has been removed [44].”
Result
The relationship between sleep quality and emotional modulation of spinal, supraspinal, and perceptual measures of pain
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“Sleep deprivation disturbs the pain inhibitory system and increases the pain sensitivity to cold and pressure (Staffe et al., 2019).”
Background
Distress and Sensitization as Main Mediators of Severity in Women with Fibromyalgia: A Structural Equation Model
Liew, B. X. W., Valera‐Calero, J. A., Varol, U., Nijs, J., Arendt‐Nielsen, L., Plaza‐Manzano, G., & Fernández‐de‐las‐Peñas, C. (2022) · Biomedicines · doi:10.3390/biomedicines10051188 · Cited by 12
“Furthermore, poor sleep impairs descending pain modulation, which may cause widespread sensitization [38].”
Background
The Effects of Recovery Sleep on Experimental Pain
Stroemel-Scheder, C., & Lautenbacher, S. (2022) · Journal of Pain · doi:10.1016/j.jpain.2022.10.009 · Cited by 11
Combining Ozonated Autohemotherapy with Pharmacological Therapy for Comorbid Insomnia and Myofascial Pain Syndrome: A Prospective Randomized Controlled Study
Shen, W., Liu, N., Ji, Z., Fang, H., Liu, F., Zhang, W. Y., Yu, X., Wang, M., Zhang, J., & Wang, X. (2022) · Pain Research and Management · doi:10.1155/2022/3562191 · Cited by 11
The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia
Lima, D., Pacheco‐Barrios, K., Slawka, E., Camargo, L., Castelo-Branco, L. E. C., Cardenas‐Rojas, A., Neto, M. S., & Fregni, F. (2023) · Pain Medicine · doi:10.1093/pm/pnad076 · Cited by 10
Neuroplasticity in the pathogenesis and treatment of chronic pain syndrome: new research and therapeutic perspectives
Lysetskyi, B., Kobyletskyi, O., Shchybovyk, D., Zubova, M., & Litvin, O. (2024) · Futurity Medicine. · doi:10.57125/fem.2024.03.30.05 · Cited by 9
Simultaneous measurement of intra-epidermal electric detection thresholds and evoked potentials for observation of nociceptive processing following sleep deprivation
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
“Another recent study demonstrated impaired conditioned pain modulation and facilitation of temporal pain summation following 24 h of total sleep deprivation in healthy subjects (Staffe et al. 2019).”
Background
Differential Gene Expression in Brain and Liver Tissue of Wistar Rats after Rapid Eye Movement Sleep Deprivation
Pandey, A., Oliver, R., & Kar, S. K. (2020) · Clocks & Sleep · doi:10.3390/clockssleep2040033 · Cited by 9
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
Neuro-Nutritional Approach to Neuropathic Pain Management: A Critical Review
Cominelli, G., Sulas, F., Pinto, D., Rinaldi, F., Favero, G., & Rezzani, R. (2025) · Nutrients · doi:10.3390/nu17091502 · Cited by 10
Global research on cancer and sleep: A bibliometric and visual analysis of the last two decades
Sun, J., Wang, C., Hui, Z., Han, W., Wang, X., & Wang, M. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1139746 · Cited by 8
Poor quality of sleep and musculoskeletal pains among highly trained and elite athletes in Senegal
Ndongo, J. M., Lele, E. C. B., Ahmet, H. M. M., Guessogo, W. R., Wiliam, M. B., Guyot, J., Rozand, V., Ahmadou, Ayina, C. N. A., Foko, L. P. K., et al. (2024) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-023-00705-4 · Cited by 8
“Based on physiological justifications, poor sleep is accompanied by an increased sensitivity to noxious stimuli and a decrease in endogenous pain-inhibitory [46–48].”
Background
The Endogenous Pain Modulatory System as a Healing Mechanism: A Proposal on How to Measure and Modulate It
de Melo, P. S., Pacheco‐Barrios, K., Marduy, A., Vásquez-Ávila, K., Simis, M., Imamura, M., Cardenas‐Rojas, A., Navarro‐Flores, A., Battistella, L. R., & Fregni, F. (2024) · NeuroSci · doi:10.3390/neurosci5030018 · Cited by 10
“Staffe et al., 2019 described a significant disruption of CPM and an increase in temporal summation in patients with sleep deprivation [70].”
Background
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
Changes in pain, daily occupations, lifestyle, and health following an occupational therapy lifestyle intervention: a secondary analysis from a feasibility study in patients with chronic high-impact pain
Nielsen, S. S., Skou, S. T., Larsen, A. E., Polianskis, R., Arendt-Nielsen, L., Østergaard, A. S., Kjær-Staal Petersen, K., Vægter, H. B., Søndergaard, J., & Christensen, J. R. (2024) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2023-0043 · Cited by 7
Youth with functional abdominal pain disorders have more sleep disturbances. A school-based study
Santucci, N. R., Velasco-Benítez, C., Velasco-Suárez, D. A., King, C., Byars, K. C., Dye, T., Li, J., & Saps, M. (2024) · Neurogastroenterology and Motility · doi:10.1111/nmo.14992 · Cited by 8
“Previous studies have indicated that poor sleep can also exacerbate pain and intensify existing pain conditions [36].”
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
“…and Woolf 2009), which indicates that the current results reflect attenuated (Eichhorn et al. 2018; Simpson et al. 2018; Smith et al. 2019; Staffe et al. 2019), even though the effects are inconsistent across studies (Babiloni et al. 2020; Herrero Babiloni et al. 2024; Rouhi et al. 2023).”
Influential
Mechanisms of the Native American pain inequity: predicting chronic pain onset prospectively at 5 years in the Oklahoma Study of Native American Pain Risk
Rhudy, J. L., Kell, P. A., Brown, T. V., Ventresca, H. M., Vore, C. N., Trevino, K. N., Jones, B. W., Lowe, T. S., & Shadlow, J. O. (2024) · Pain · doi:10.1097/j.pain.0000000000003442 · 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
Spontaneous Pain and Pain Sensitivity in Response to Prolonged Experimental Sleep Disturbances—Potential Sex Differences
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.”
Efficacy and Safety of Preoperative Melatonin for Women Undergoing Cesarean Section: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials
Albzea, W., Almonayea, L., Aljassar, M., Atmeh, M., Sadder, K. A. A., Alqattan, Y., Alhajaji, R., AlNadwi, H., Alnami, I., & Alhajaji, F. (2023) · Medicina · doi:10.3390/medicina59061065 · Cited by 5
UK medical cannabis registry: A clinical outcome analysis of medical cannabis therapy in chronic pain patients with and without co‐morbid sleep impairment
Datta, I., Erridge, S., Holvey, C., Coomber, R., Guru, R., Holden, W., Medniuk, A. D., Sajad, M., Searle, R. D., Usmani, A., et al. (2024) · Pain Practice · doi:10.1111/papr.13438 · Cited by 5
Shoulder pain phenotyping: A guide for clinicians to determine predominant nociceptive, neuropathic, or nociplastic shoulder pain
Baets, L. D., Kuppens, K., Labie, C., Haik, M. N., Kapreli, E., Bilika, P., Struyf, F., Borms, D., Fernández‐de‐las‐Peñas, C., Kosek, E., et al. (2025) · Brazilian Journal of Physical Therapy · doi:10.1016/j.bjpt.2025.101240 · Cited by 5
“88 This suggests that different underlying mechanisms are responsible for altered pain modulation, and that these influential factors might need consideration in diagnostic criteria for pain phenotyping.”
Acute sleep deprivation induces hyperalgesia through P2X4-mediated microglial activation in mice
Huang, S., Cheng, W., Lai, P., Liu, X., Peng, S., Yang, X., & Du, X. (2025) · European journal of medical research · doi:10.1186/s40001-025-03326-4 · Cited by 5
Exercise-Induced Hypoalgesia in Patients with Chronic Whiplash-Associated Disorders: Differences between Subgroups Based on the Central Sensitization Inventory
Hendriks, E. P., Coppieters, I., Voogt, L. P., Cools, W., & Ickmans, K. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13020482 · Cited by 5
“Temporal summation was assessed by the application of a series of short noxious stimuli, believed to represent the wind-up physiological phenomenon and interpreted as the gradual increase in pain sensitivity when continuously exposed to stimuli with a constant intensity [71,72].”
Method
Evidence-Based Opinions from Multidisciplinary Experts on Use of Naturopathic Herbal Remedies in Pain Management
Mobasheri, A., Spring-Charles, A., Gamaleri, F. C., McSwan, J., Garg, M. L., & Sethi, V. S. (2024) · Journal of Pain Research · doi:10.2147/jpr.s432090 · Cited by 5
A simple, bed-side tool to assess evoked pressure pain intensity
Hostrup, S. N., O’Neill, S. F. D., Larsen, J. B., Arendt‐Nielsen, L., & Petersen, K. K. (2022) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2022-0055 · Cited by 7
Impact of Anxiety Levels and Sleep Patterns on Perceived Pain During Intravitreal Bevacizumab Injections
Wieder, M. S., Szlechter, M., Fischman, N., Inker, S., Rusu, I., & Mbekeani, J. N. (2021) · Ophthalmic surgery, lasers & imaging retina · doi:10.3928/23258160-20210819-02 · Cited by 5
A crossover study evaluating the sex‐dependent and sensitizing effects of sleep deprivation using a nociceptive test battery in healthy subjects
Hijma, H. J., Koopmans, I. W., Klaassen, E. S., Doll, R. J., Zuiker, R. G. J. A., & Groeneveld, G. J. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15505 · Cited by 6
Insomnia and short sleep duration, but not chronotype, is associated with chronic widespread pain: Mendelian randomization study
Williams, J., Hum, R. M., Alam, U., & Zhao, S. S. (2024) · Rheumatology International · doi:10.1007/s00296-024-05636-y · Cited by 6
“This facilitates spinal excitability and sensitisation of peripheral pathways to cold and pressure pain [25 ].”
Mediation of the frailty index, the relationship between sleep duration and chronic pain in different body regions: insights from the CHARLS cross-sectional study
Li, C., Ding, H., Zhang, L., Ma, C., Ma, C., Wen, H., & Zhao, X. (2025) · Journal of Orthopaedic Surgery and Research · doi:10.1186/s13018-025-06157-5 · Cited by 4
“These findings underscore the importance of getting adequate sleep to maintaining the body’s natural pain inhibition processes and suggest that sleep therapy might help normalize pain sensitivity in individuals who experience sleep deprivation [41].”
Patient Sleep Quality in Acute Inpatient Rehabilitation
Davis, S. M., Mekany, M. A., Kim, J. J., & Han, J. J. (2021) · PM&R · doi:10.1002/pmrj.12550 · Cited by 4
“5 days (3-53) Impairment Group Code diagnosis Amputation 3”
Background
Analgesic efficacy of a portable, disposable, and self‐applied transcutaneous electrical nerve stimulation device during migraine attacks: A real‐life randomized controlled trial
Domingues, F. S., Gayoso, M. V., Sikandar, S., da Silva, L. M., Fonseca, R. G., & de Barros, G. A. M. (2021) · Pain Practice · doi:10.1111/papr.13042 · Cited by 4
“Sleeprelated outcomes should be evaluated in future studies as this may also be biologically linked to improvement in pain sensitization through functional activity of midbrain structures.(37) Other limitations of this study include the low number of male participants, and the low overall number of patients.”
Background
Differential pain perception among females with or without nonspecific chronic low back pain and comorbid insomnia: a quantitative sensory testing analysis
Chang, J. R., Kwan, R. L., Sun, E. R., Li, S. X., Liang, P., Liu, J. Q., Zheng, D. K. Y., Zhou, Z., Huang, F. F.-Y., Samartzis, D., et al. (2025) · Pain · doi:10.1097/j.pain.0000000000003591 · Cited by 4
Optimizing an automated sleep detection algorithm using wrist-worn accelerometer data for individuals with chronic pain
Faust, L. J., Fortune, E., Jahanian, O., Oloyede, S. V., Trouard, C., Dixon, S., Torres, E., Sletten, C., & Scholten, P. (2025) · PLoS ONE · doi:10.1371/journal.pone.0319348 · Cited by 3
Digitally delivered cognitive behavioral therapy for insomnia (CBT-I) for patients with chronic pain and insomnia (The Back2Sleep Trial): study protocol for a randomized controlled trial
Olsen, M. L. S., Thorlund, J. B., Zachariae, R. H., Vach, W., Bendix, L., Jespersen, J. R., Kidmose, P., Parsons, C. E., Kidholm, K., & Vægter, H. B. (2025) · Trials · doi:10.1186/s13063-025-09013-3 · Cited by 3
“One night with disturbed sleep has been found to reduce pain thresholds and impair the pain-inhibitory function in healthy individuals [4], and several population-based studies have demonstrated negative effects of insomnia on pain and found links between sleep disturbance and chronic…”
Pain Sensitization and Descending Pain Inhibition in Fibromyalgia
Garcia-Hernandez, A., de la Coba, P., Bruehl, S. P., Duschek, S., & del Paso, G. A. R. (2025) · Clinical Journal of Pain · doi:10.1097/ajp.0000000000001327 · Cited by 4
The Effect of Spinal Muscle Fatigue and Psychosocial Factors on Pressure-Pain Threshold in Healthy Adults
Mais, S., & Smith, J. A. (2023) · Pain Research and Management · doi:10.1155/2023/7336477 · Cited by 3
Responders and nonresponders to topical capsaicin display distinct temporal summation of pain profiles
Wong, F. Y. K., Reddy, A., Rho, Y., Vollert, J., Strutton, P. H., & Hughes, S. (2023) · PAIN Reports · doi:10.1097/pr9.0000000000001071 · Cited by 3
“The higher baseline TSP scores could be a result of cortical influences on descending pain modulation systems; day-to-day fluctuations in levels of sleep and cognitive and affective processing can exert top-down influences on spinally projecting pain modulation networks.(25,31) It is possible that by screening partici…”
Background
The potential effect of walking on quantitative sensory testing, pain catastrophizing, and perceived stress: an exploratory study
Rasmussen, A. H., Petersen, L. K., Sperling, M. K., Bertelsen, M. M., Rathleff, M. S., & Petersen, K. K. (2023) · Scandinavian Journal of Pain · doi:10.1515/sjpain-2023-0039 · Cited by 3
Cervical Cobb angle, sleep quality and psychological factors in patients with chronic neck pain with and without cervicogenic headache
Aldabbas, M. M., & Alshana, O. N. (2025) · European Journal of Physiotherapy · doi:10.1080/21679169.2025.2466041 · Cited by 3
“…to physiotherapy treatment plans in patients with ceh, especially when the psychosocial factors and symptoms of central sensitisation are present [43]. also, psychosocial factors such as anxiety and depression are well-established risk for the transition from acute to chronic pain, commonly seen…”
Sleep Problems Mediate the Relationship Between Psychosocial Stress and Pain Facilitation in Native Americans: A Structural Equation Modeling Analysis from the Oklahoma Study of Native American Pain Risk
Kell, P. A., Huber, F. A., Street, E. N., Shadlow, J. O., & Rhudy, J. L. (2022) · Annals of Behavioral Medicine · doi:10.1093/abm/kaac034 · Cited by 3
Prevalence and Predictors of Leg Cramps in the Third Trimester of Pregnancy: A Cross-Sectional Study
Abandeh, A., Sindiani, A., Nazzal, M. S., Almasri, N. A., Megdadi, A., Morris, L. D., Alshdaifat, E., & Kanaan, S. F. (2024) · International Journal of Women s Health · doi:10.2147/ijwh.s465872 · Cited by 2
“34 Therefore, there is a need to develop a practical guideline to evaluate and treat sleep disturbances in pregnant women.”
Background
Estradiol is Pro-Nociceptive and Associated with a Small-Fiber Neuropathy Among Premenopausal Women with Sickle Cell Disease
Ramsay, Z., Sharma, D., Wisdom‐Phipps, M., Chin, N., Campbell, L., Knight‐Madden, J., & Asnani, M. (2025) · Hemoglobin · doi:10.1080/03630269.2025.2489634 · Cited by 2
Randomised, controlled clinical trial evaluating the effects of preoperative insomnia treatment on postoperative pain control and recovery: a protocol for the Promoting Sleep to Alleviate Pain-Arthroplasty (PROSAP-A) trial
Bjurström, M. F., Bothelius, K., Maathz, P., Jernelöv, S., Kraepelien, M., Rosenström, A. H. C., Niklasson, A., Smith, M. T., Olmstead, R., Irwin, M. R., et al. (2025) · BMJ Open · doi:10.1136/bmjopen-2025-099785 · Cited by 2
Found in translation: orexin receptor antagonism for the treatment of opioid use disorder
Raymond, J. S., Vareed, R. D., Peters, J., & James, M. H. (2025) · Translational Psychiatry · doi:10.1038/s41398-025-03571-5 · Cited by 2
“Clinical evidence also supports a bidirectional interaction between sleep and pain [122]; sleep disturbance can contribute to hyperalgesia [123 – 125] and sleep disturbances are highly prevalent in individuals experiencing chronic pain [126, 127].”
TUALANG HONEY MODULATED NOCICEPTIVE RESPONSES IN THE THALAMUS OF REM SLEEP DEPRIVATION RAT MODEL
Shafie, A. S. M., Aziz, C. B. A., Noordin, L., Long, I., Zin, A. A. M., & Siran, R. (2021) · Malaysian Applied Biology · doi:10.55230/mabjournal.v50i3.2216 · Cited by 2
“Patients with chronic pain syndromes often suffer from insomnia (Morin et al., 1998) and a report has demonstrated that healthy individuals with sleep deprivation had increased pain intensity (Staffe et al., 2019).”
Background

Authors: Staffe, A. T., Bech, M. W., Clemmensen, S. L. K., Nielsen, H. T., Larsen, D. B., & Petersen, K. K.
Affiliations: Aalborg University (DK)
Corresponding author: Petersen, Kristian Kjær
ORCID: Staffe, Alexander Torp
Bech, Mathias Winther
Larsen, Dennis Boye
Petersen, Kristian Kjær
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2019-12-04
Volume: 14
Issue: 12
Pages: e0225849
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0225849
PMC: PMC6892491
OpenAlex: W2991704716
Cited by: 150
References: 70
Citations by year: 2026: 22 · 2025: 30 · 2024: 21 · 2023: 22 · 2022: 25 · 2021: 22 · 2020: 6 · 2019: 1
FWCI: 9.23
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: PLoS ONE (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: Danmarks Grundforskningsfond (DNRF121)
Aalborg Universitet (771126)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords: total sleep deprivation, pain sensitivity, conditioned pain modulation, temporal summation, descending pain modulation, thermal pain, pressure pain, cold pain, pain detection threshold, pain tolerance, spinal cord excitability, chronic pain, insomnia, sleep therapy
MeSH terms: Adult, Denmark, Female, Humans, Male, Pain Measurement, Sleep, Sleep Deprivation, Thermosensing, Pain Threshold, Young Adult, Public Health Surveillance

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Total sleep deprivation increases pain sensitivity, impairs conditioned pain modulation and facilitates temporal summation of pain in healthy participants

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