Orofacial pain/headache interlaced to insomnia, sleep apnea and periodic limb movement during sleep/restless leg syndrome: a critical and comprehensive review with insights into social determinants

This critical review explores the intricate interaction between orofacial pain and headache disorders and three prevalent sleep disorders: insomnia, obstructive sleep apnea (OSA) and periodic limb movements (PLMs) during sleep, while integrating the role of social determinants of health. Orofacial pain conditions, including temporomandibular disorders (TMD), headache, and burning mouth syndrome, frequently co-occur with sleep disturbances, creating a bidirectional cycle where poor sleep exacerbates pain and vice versa. The mechanisms underlying this relationship involve disrupted restorative sleep, neuroinflammation, heightened arousal and impaired descending pain modulation. Importantly, social factors such as socioeconomic status, healthcare access, education level, and social support influence the prevalence, severity, and management of these comorbidities, contributing to significant disparities in outcomes. We present recent advances in the phenotyping and endotyping of individuals with sleep-pain comorbidities, which aim to identify subgroups with shared characteristics to guide personalized interventions, emphasizing the need for interdisciplinary approaches that bridge dentistry, sleep medicine and public health to address the multifactorial nature of these conditions. Practical considerations for clinicians managing these patients are discussed, including screening tools, treatment modalities and the impact of social context. Future research directions prioritize the integration of measures of social factors into study designs, advancing personalized medicine and employing innovative technologies to better understand genotypes and phenotypes involved in pain perception and sleep characteristics, and manage the interplay between sleep and orofacial pain. The goal of addressing the interaction between sleep and pain is to improve health equity and optimize outcomes for individuals affected by these interrelated conditions.

COMISA; Management; Orexin; Pain; Sleep; Social determinants

[1] Choy EHS. The role of sleep in pain and fibromyalgia. Nature Reviews Rheumatology. 2015; 11: 513–520.

[2] Lavigne GJ, Nashed A, Manzini C, Carra MC. Does sleep differ among patients with common musculoskeletal pain disorders? Current Rheumatology Reports. 2011; 13: 535–542.

[3] Lavigne GJ, Sessle BJ. The neurobiology of orofacial pain and sleep and their interactions. Journal of Dental Research. 2016; 95: 1109–1116.

[4] Benoliel R, Zini A, Zakuto A, Slutzky H, Haviv Y, Sharav Y, et al. Subjective sleep quality in temporomandibular disorder patients and association with disease characteristics and oral health-related quality of life. Journal of Oral & Facial Pain and Headache. 2017; 31: 313–322.

[5] Almoznino G, Benoliel R, Sharav Y, Haviv Y. Sleep disorders and chronic craniofacial pain: characteristics and management possibilities. Sleep Medicine Reviews. 2017; 33: 39–50.

[6] Benoliel R, Eliav E, Sharav Y. Self-reports of pain-related awakenings in persistent orofacial pain patients. Journal of Orofacial Pain. 2009; 23: 330–338.

[7] Burr MR, Naze GS, Shaffer SM, Emerson AJ. The role of sleep dysfunction in temporomandibular onset and progression: a systematic review and meta-analyses. Journal of Oral Rehabilitation. 2021; 48: 183–194.

[8] Chisci D, Parrini S, Baldini N, Chisci G. Patterns of third-molar-pericoronitis-related pain: a morphometrical observational retrospective study. Healthcare. 2023; 11: 1890.

[9] Al-Madani SO, Jaber M, Prasad P, Maslamani MJMA. The patterns of impacted third molars and their associated pathologies: a retrospective observational study of 704 patients. Journal of Clinical Medicine. 2024; 13: 330.

[10] Finan PH, Goodin BR, Smith MT. The association of sleep and pain: an update and a path forward. The Journal of Pain. 2013; 14: 1539–1552.

[11] Klyne DM, Hall M. Is sleep the new treatment for pain? Two issues need resolving before deciding. Sleep. 2024; 47: zsae089.

[12] Klyne DM, Smith SS, Hall M. Should cognitive behavioral therapy for insomnia be considered for preventing and managing chronic pain? Sleep. 2024; 47: zsae177.

[13] Herrero Babiloni A, Beetz G, Tang NKY, Heinzer R, Nijs J, Martel MO, et al. Towards the endotyping of the sleep–pain interaction: a topical review on multitarget strategies based on phenotypic vulnerabilities and putative pathways. Pain. 2021; 162: 1281–1288.

[14] Michelotti A, Liguori R, Toriello M, D’Antò V, Vitale D, Castaldo G, et al. Catechol-O-methyltransferase (COMT) gene polymorphisms as risk factor in temporomandibular disorders patients from Southern Italy. The Clinical Journal of Pain. 2014; 30: 129–133.

[15] Lerman SF, Mun CJ, Hunt CA, Kunatharaju S, Buenaver LF, Finan PH, et al. Insomnia with objective short sleep duration in women with temporomandibular joint disorder: quantitative sensory testing, inflammation and clinical pain profiles. Sleep Medicine. 2022; 90: 26–35.

[16] Slade GD, Sanders AE, Ohrbach R, Fillingim RB, Dubner R, Gracely RH, et al. Pressure pain thresholds fluctuate with, but do not usefully predict, the clinical course of painful temporomandibular disorder. Pain. 2014; 155: 2134–2143.

[17] Suzuki H, Tahara S, Mitsuda M, Funaba M, Fujimoto K, Ikeda H, et al. Reference intervals and sources of variation of pressure pain threshold for quantitative sensory testing in a Japanese population. Scientific Reports. 2023; 13: 13043.

[18] Saxer F, Hollinger A, Bjurström MF, Conaghan PG, Neogi T, Schieker M, et al. Pain-phenotyping in osteoarthritis: current concepts, evidence, and considerations towards a comprehensive framework for assessment and treatment. Osteoarthritis and Cartilage Open. 2024; 6: 100433.

[19] Herrero Babiloni A, Jodoin M, Provost C, Charlebois-Plante C, De Koninck BP, Apinis-Deshaies A, et al. Females with painful temporomandibular disorders present higher intracortical facilitation relative to pain-free controls. Clinical Oral Investigations. 2023; 28: 12.

[20] Lavigne GJ, Herrero Babiloni A, Beetz G, Dal Fabbro C, Sutherland K, Huynh N, et al. Critical issues in dental and medical management of obstructive sleep apnea. Journal of Dental Research. 2020; 99: 26–35.

[21] Park CO, Kim SM, Lee KH, Bieber T. Biomarkers for phenotype-endotype relationship in atopic dermatitis: a critical review. EBioMedicine. 2024; 103: 105121.

[22] Sanchez-Pinto LN, Stroup EK, Pendergrast T, Pinto N, Luo Y. Derivation and validation of novel phenotypes of multiple organ dysfunction syndrome in critically ill children. JAMA Network open. 2020; 3: e209271.

[23] Vaara ST, Bhatraju PK, Stanski NL, McMahon BA, Liu K, Joannidis M, et al. Subphenotypes in acute kidney injury: a narrative review. Critical Care. 2022; 26: 251.

[24] Caminati M, Senna G, Maule M, Di Sabatino A, Rossi CM. Diagnosis, management and therapeutic options for eosinophilic esophagitis. Current Opinion in Allergy & Clinical Immunology. 2024; 24: 122–128.

[25] Radojčić MR, Chen L. Editorial: musculoskeletal pain phenotypes and personalised pain medicine. Frontiers in Pain Research. 2024; 5: 1481839.

[26] Walker DOH, Rabelo VC, Stewart OJ, Herbert DN. Social determinants of mental health: the roles of traumatic events, financial strain, housing instability, food insecurity, and commute time. Journal of American College Health. 2024; 72: 3591–3602.

[27] Kapos FP, Craig KD, Anderson SR, Bernardes SF, Hirsh AT, Karos K, et al. Social determinants and consequences of pain: toward multilevel, intersectional, and life course perspectives. The Journal of Pain. 2024; 25: 104608.

[28] Jean-Louis G, Grandner MA, Seixas AA. Social determinants and health disparities affecting sleep. The Lancet Neurology. 2022; 21: 864–865.

[29] Rethorn ZD, Cook C, Reneker JC. Social determinants of health: if you aren’t measuring them, you aren’t seeing the big picture. The Journal of Orthopaedic and Sports Physical Therapy. 2019; 49: 872–874.

[30] Tang NK, Goodchild CE, Sanborn AN, Howard J, Salkovskis PM. Deciphering the temporal link between pain and sleep in a heterogeneous chronic pain patient sample: a multilevel daily process study. Sleep. 2012; 35: 675–687A.

[31] Bean DJ, Horne J, Lee AC, Johnson MH. Pre-sleep cognitive arousal exacerbates sleep disturbance in chronic pain: an exploratory daily diary and actigraphy study. Scandinavian Journal of Pain. 2021; 21: 724–731.

[32] Andersen ML, Araujo P, Frange C, Tufik S. Sleep disturbance and pain: a tale of two common problems. Chest. 2018; 154: 1249–1259.

[33] Gerhart JI, Burns JW, Post KM, Smith DA, Porter LS, Burgess HJ, et al. Relationships between sleep quality and pain-related factors for people with chronic low back pain: tests of reciprocal and time of day effects. Annals of Behavioral Medicine. 2017; 51: 365–375.

[34] Lucena L, Lavigne G, Fabbro CD, Andersen ML, Tufik S, Hachul H. Association between night pain and quality of life in women: a general population sleep study. European Journal of Pain. 2023; 27: 401–412.

[35] Frange C, Hachul H, Hirotsu C, Tufik S, Andersen ML. Temporal analysis of chronic musculoskeletal pain and sleep in postmenopausal women. Journal of Clinical Sleep Medicine. 2019; 15: 223–234.

[36] Paquet J, Kawinska A, Carrier J. Wake detection capacity of actigraphy during sleep. Sleep. 2007; 30: 1362–1369.

[37] Smith MT, McCrae CS, Cheung J, Martin JL, Harrod CG, Heald JL, et al. Use of actigraphy for the evaluation of sleep disorders and circadian rhythm sleep-wake disorders: an American academy of sleep medicine clinical practice guideline. Journal of Clinical Sleep Medicine. 2018; 14: 1231–1237.

[38] Marino M, Li Y, Rueschman MN, Winkelman JW, Ellenbogen JM, Solet JM, et al. Measuring sleep: accuracy, sensitivity, and specificity of wrist actigraphy compared to polysomnography. Sleep. 2013; 36: 1747–1755.

[39] Bentley AJ, Newton S, Zio CD. Sensitivity of sleep stages to painful thermal stimuli. Journal of Sleep Research. 2003; 12: 143–147.

[40] Chouchou F, Dang-Vu TT, Rainville P, Lavigne G. The role of sleep in learning placebo effects. International Review of Neurobiology. 2018; 139: 321–355.

[41] Lavigne G, Zucconi M, Castronovo C, Manzini C, Marchettini P, Smirne S. Sleep arousal response to experimental thermal stimulation during sleep in human subjects free of pain and sleep problems. Pain. 2000; 84: 283–290.

[42] Lavigne G, Brousseau M, Kato T, Mayer P, Manzini C, Guitard F, et al. Experimental pain perception remains equally active over all sleep stages. Pain. 2004; 110: 646–655.

[43] Muzet A, Schieber JP, Ehrhart J, Lienhard JP. Phases of transitory activation and the changes of electroencephalographic stages of sleep. Revue d’Electroencéphalographie et de Neurophysiologie Clinique. 1973; 3: 219–222. (In French)

[44] Parrino L, Zucconi M, Terzano GM. Sleep frangmentation and arousal in the pain patient. In Lavigne G, Sessle BJ (eds.) Sleep and pain (pp. 213–234). 1st edn. IASP Press: Seattle. 2007.

[45] Terzano MG, Parrino L, Sherieri A, Chervin R, Chokroverty S, Guilleminault C, et al. Atlas, rules, and recording techniques for the scoring of cyclic alternating pattern (CAP) in human sleep. Sleep Medicine. 2001; 2: 537–553.

[46] Rizzi M, Sarzi-Puttini P, Atzeni F, Capsoni F, Andreoli A, Pecis M, et al. Cyclic alternating pattern: a new marker of sleep alteration in patients with fibromyalgia? The Journal of Rheumatology. 2004; 31: 1193–1199.

[47] Rizzi M, Radovanovic D, Santus P, Airoldi A, Frassanito F, Vanni S, et al. Influence of autonomic nervous system dysfunction in the genesis of sleep disorders in fibromyalgia patients. Clinical and Experimental Rheumatology. 2017; 35: 74–80.

[48] Edwards RR, Almeida DM, Klick B, Haythornthwaite JA, Smith MT. Duration of sleep contributes to next-day pain report in the general population. Pain. 2008; 137: 202–207.

[49] Xu C, Ren X, Lin P, Jin S, Zhang Z. Exploring the causal effects of sleep characteristics on TMD-related pain: a two-sample Mendelian randomization study. Clinical Oral Investigations. 2024; 28: 384.

[50] Jiang Y, Yu M, Gong X, Zhao Y, Gao X. Association of night-time sleep and daytime napping with painful temporomandibular disorder. Journal of Oral Rehabilitation. 2024; 51: 1981–1988.

[51] Lavigne GJ, Okura K, Abe S, Colombo R, Huynh N, Montplaisir JY, et al. Gender specificity of the slow wave sleep lost in chronic widespread musculoskeletal pain. Sleep Medicine. 2011; 12: 179–185.

[52] Haack M, Mullington JM. Sustained sleep restriction reduces emotional and physical well-being. Pain. 2005; 119: 56–64.

[53] Simpson NS, Scott-Sutherland J, Gautam S, Sethna N, Haack M. Chronic exposure to insufficient sleep alters processes of pain habituation and sensitization. Pain. 2018; 159: 33–40.

[54] Smith MT, Edwards RR, McCann UD, Haythornthwaite JA. The effects of sleep deprivation on pain inhibition and spontaneous pain in women. Sleep. 2007; 30: 494–505.

[55] Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep. 2006; 29: 145–151.

[56] Onen SH, Alloui A, Gross A, Eschallier A, Dubray C. The effects of total sleep deprivation, selective sleep interruption and sleep recovery on pain tolerance thresholds in healthy subjects. Journal of Sleep Research. 2001; 10: 35–42.

[57] Schrimpf M, Liegl G, Boeckle M, Leitner A, Geisler P, Pieh C. The effect of sleep deprivation on pain perception in healthy subjects: a meta-analysis. Sleep Medicine. 2015; 16: 1313–1320.

[58] Irwin MR, Olmstead R, Bjurstrom MF, Finan PH, Smith MT. Sleep disruption and activation of cellular inflammation mediate heightened pain sensitivity: a randomized clinical trial. Pain. 2023; 164: 1128–1137.

[59] Herrero Babiloni A, Baril AA, Charlebois-Plante C, Jodoin M, Sanchez E, De Baets L, et al. The putative role of neuroinflammation in the interaction between traumatic brain injuries, sleep, pain and other neuropsychiatric outcomes: a state-of-the-art review. Journal of Clinical Medicine. 2023; 12: 1793.

[60] Krause AJ, Prather AA, Wager TD, Lindquist MA, Walker MP. The pain of sleep loss: a brain characterization in humans. The Journal of Neuroscience. 2019; 39: 2291–2300.

[61] Herrero Babiloni A, De Koninck BP, Beetz G, De Beaumont L, Martel MO, Lavigne GJ. Sleep and pain: recent insights, mechanisms, and future directions in the investigation of this relationship. Journal of Neural Transmission. 2020; 127: 647–660.

[62] Smith MT III, Remeniuk B, Finan PH, Speed TJ, Tompkins DA, Robinson M, et al. Sex differences in measures of central sensitization and pain sensitivity to experimental sleep disruption: implications for sex differences in chronic pain. Sleep. 2019; 42: zsy209.

[63] Eichhorn N, Treede RD, Schuh-Hofer S. The role of sex in sleep deprivation related changes of nociception and conditioned pain modulation. Neuroscience. 2018; 387: 191–200.

[64] Herrero Babiloni A, Brazeau D, Jodoin M, Theis-Mahon N, Martel MO, Lavigne GJ, et al. The impact of sleep disturbances on endogenous pain modulation: a systematic review and meta-analysis. The Journal of Pain. 2024; 25: 875–901.

[65] Rouhi S, Topcu J, Egorova-Brumley N, Jordan AS. The impact of sleep disturbance on pain perception: a systematic review examining the moderating effect of sex and age. Sleep Medicine Reviews. 2023; 71: 101835.

[66] Stroemel-Scheder C, Karmann AJ, Ziegler E, Heesen M, Knippenberg-Bigge K, Lang PM, et al. Sleep, experimental pain and clinical pain in patients with chronic musculoskeletal pain and healthy controls. Journal of Pain Research. 2019; 12: 3381–3393.

[67] Yin M, Muhammed SA, Wang Y, Colloca L. Yoga and massage are associated with small experimental placebo effects in chronic orofacial pain. European Journal of Pain. 2023; 27: 816–830.

[68] Okusogu C, Wang Y, Akintola T, Haycock NR, Raghuraman N, Greenspan JD, et al. Placebo hypoalgesia: racial differences. Pain. 2020; 161: 1872–1883.

[69] Olson EM, Akintola T, Phillips J, Blasini M, Haycock NR, Martinez PE, et al. Effects of sex on placebo effects in chronic pain participants: a cross-sectional study. Pain. 2021; 162: 531–542.

[70] Laverdure-Dupont D, Rainville P, Renancio C, Montplaisir J, Lavigne G. Placebo analgesia persists during sleep: an experimental study. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2018; 85: 33–38.

[71] Chouchou F, Chauny JM, Rainville P, Lavigne GJ. Selective REM Sleep deprivation improves expectation-related placebo analgesia. PLOS ONE. 2015; 10: e0144992.

[72] Wang Y, Chan E, Dorsey SG, Campbell CM, Colloca L. Who are the placebo responders? A cross-sectional cohort study for psychological determinants. Pain. 2022; 163: 1078–1090.

[73] Herrero Babiloni A, Provost C, Charlebois-Plante C, De Koninck BP, Apinis-Deshaies A, De Beaumont L, et al. The contribution of sleep quality and psychological factors to the experience of within-day pain fluctuations among individuals with temporomandibular disorders. The Journal of Pain. 2024; 25: 104576.

[74] Gottlieb DJ, Punjabi NM. Diagnosis and management of obstructive sleep apnea: a review. JAMA. 2020; 323: 1389–1400.

[75] Theadom A, Cropley M, Kantermann T. Daytime napping associated with increased symptom severity in fibromyalgia syndrome. BMC Musculoskeletal Disorders. 2015; 16: 13.

[76] Parimi N, Blackwell T, Stone KL, Lui LY, Ancoli-Israel S, Tranah GJ, et al.; Study of Osteoporotic Fractures Study Group. Hip pain while using lower extremity joints and sleep disturbances in elderly white women: results from a cross-sectional analysis. Arthritis Care & Research. 2012; 64: 1070–1078.

[77] Conley S, Feder SL, Jeon S, Redeker NS. Daytime and nighttime sleep characteristics and pain among adults with stable heart failure. The Journal of Cardiovascular Nursing. 2019; 34: 390–398.

[78] Foley DJ, Vitiello MV, Bliwise DL, Ancoli-Israel S, Monjan AA, Walsh JK. Frequent napping is associated with excessive daytime sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. The American Journal of Geriatric Psychiatry. 2007; 15: 344–350.

[79] Faraut B, Léger D, Medkour T, Dubois A, Bayon V, Chennaoui M, et al. Napping reverses increased pain sensitivity due to sleep restriction. PLOS ONE. 2015; 10: e0117425.

[80] Simonelli G, Mantua J, Gad M, St Pierre M, Moore L, Yarnell AM, et al. Sleep extension reduces pain sensitivity. Sleep Medicine. 2019; 64: 172–176.

[81] Faraut B, Andrillon T, Vecchierini MF, Leger D. Napping: a public health issue. From epidemiological to laboratory studies. Sleep Medicine reviews. 2017; 35: 85–100.

[82] Patterson PD, Liszka MK, Mcilvaine QS, Nong L, Weaver MD, Turner RL, et al. Does the evidence support brief (≤30-mins), moderate (31–60-mins), or long duration naps (61+ mins) on the night shift? A systematic review. Sleep Medicine Reviews. 2021; 59: 101509.

[83] Takahashi M. The role of prescribed napping in sleep medicine. Sleep Medicine Reviews. 2003; 7: 227–235.

[84] Fang SC, Huang CJ, Wu YL, Wu PY, Tsai PS. Effects of napping on cognitive function modulation in elderly adults with a morning chronotype: a nationwide survey. Journal of Sleep Research. 2019; 28: e12724.

[85] Yang YB, Zheng YB, Sun J, Yang LL, Li J, Gong YM, et al. To nap or not? Evidence from a meta-analysis of cohort studies of habitual daytime napping and health outcomes. Sleep Medicine Reviews. 2024; 78: 101989.

[86] Lavigne GJ, Pires GN, Dal Fabbro C, Herrero Babiloni A, Martel MO, Morin CM, et al. Doctor, can napping help relieve my pain? Research path to assess the potential benefits/harms of napping for individuals with chronic pain. Sleep. 2024; 47: zsae043.

[87] Mathias JL, Cant ML, Burke ALJ. Sleep disturbances and sleep disorders in adults living with chronic pain: a meta-analysis. Sleep Medicine. 2018; 52: 198–210.

[88] Cunali PA, Almeida FR, Santos CD, Valdrighi NY, Nascimento LS, Dal’Fabbro C, et al. Prevalence of temporomandibular disorders in obstructive sleep apnea patients referred for oral appliance therapy. Journal of Orofacial Pain. 2009; 23: 339–344.

[89] Smith MT, Wickwire EM, Grace EG, Edwards RR, Buenaver LF, Peterson S, et al. Sleep disorders and their association with laboratory pain sensitivity in temporomandibular joint disorder. Sleep. 2009; 32: 779–790.

[90] Dahan H, Shir Y, Velly A, Allison P. Specific and number of comorbidities are associated with increased levels of temporomandibular pain intensity and duration. The Journal of Headache and Pain. 2015; 16: 528.

[91] McNamara S, Spurling BC, Bollu PC. Chronic insomnia. StatPearls: Treasure Island, FL. 2025.

[92] Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014; 146: 1387–1394.

[93] Kronholm E, Partonen T, Härmä M, Hublin C, Lallukka T, Peltonen M, et al. Prevalence of insomnia-related symptoms continues to increase in the Finnish working-age population. Journal of Sleep Research. 2016; 25: 454–457.

[94] Ohayon MM. Prevalence and correlates of nonrestorative sleep complaints. Archives of Internal Medicine. 2005; 165: 35–41.

[95] Morin CM, Drake CL, Harvey AG, Krystal AD, Manber R, Riemann D, et al. Insomnia disorder. Nature reviews. Disease Primers. 2015; 1: 15026.

[96] Bastien CH, Vallières A, Morin CM. Validation of the insomnia severity index as an outcome measure for insomnia research. Sleep Medicine. 2001; 2: 297–307.

[97] Morin CM, Belleville G, Bélanger L, Ivers H. The insomnia severity index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. 2011; 34: 601–608.

[98] Poon SH, Quek SY, Lee TS. Insomnia disorders: nosology and classification past, present, and future. The Journal of Neuropsychiatry and Clinical Neurosciences. 2021; 33: 194–200.

[99] Sun Y, Laksono I, Selvanathan J, Saripella A, Nagappa M, Pham C, et al. Prevalence of sleep disturbances in patients with chronic non-cancer pain: a systematic review and meta-analysis. Sleep Medicine Reviews. 2021; 57: 101467.

[100] Lindell M, Grimby-Ekman A. Stress, non-restorative sleep, and physical inactivity as risk factors for chronic pain in young adults: a cohort study. PLOS ONE. 2022; 17: e0262601.

[101] Herrero Babiloni A, Beetz G, Bruneau A, Martel MO, Cistulli PA, Nixdorf DR, et al. Multitargeting the sleep-pain interaction with pharmacological approaches: a narrative review with suggestions on new avenues of investigation. Sleep Medicine Reviews. 2021; 59: 101459.

[102] Bykov K, Bateman BT, Franklin JM, Vine SM, Patorno E. Association of gabapentinoids with the risk of opioid-related adverse events in surgical patients in the United States. JAMA Network Open. 2020; 3: e2031647.

[103] Almoznino G, Haviv Y, Sharav Y, Benoliel R. An update of management of insomnia in patients with chronic orofacial pain. Oral Diseases. 2017; 23: 1043–1051.

[104] Roohbakhsh A, Alavi MS, Azhdari-Zarmehri H. The orexinergic (hypocretin) system and nociception: an update to supraspinal mechanisms. Current Medicinal Chemistry. 2018; 25: 3917–3929.

[105] Razavi BM, Hosseinzadeh H. A review of the role of orexin system in pain modulation. Biomedicine & Pharmacotherapy. 2017; 90: 187–193.

[106] McDonald T, Liang HA, Sanoja R, Gotter AL, Kuduk SD, Coleman PJ, et al. Pharmacological evaluation of orexin receptor antagonists in preclinical animal models of pain. Journal of Neurogenetics. 2016; 30: 32–41.

[107] Roehrs T, Withrow D, Koshorek G, Verkler J, Bazan L, Roth T. Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo. Journal of Clinical Sleep Medicine. 2020; 16: 415–421.

[108] Ueno K, Sato H, Nomura Y, Obata N, Mizobuchi S. Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study. Pain Medicine. 2024; 25: 139–143.

[109] Rios P, Cardoso R, Morra D, Nincic V, Goodarzi Z, Farah B, et al. Comparative effectiveness and safety of pharmacological and non-pharmacological interventions for insomnia: an overview of reviews. Systematic Reviews. 2019; 8: 281.

[110] Tang NK, Lereya ST, Boulton H, Miller MA, Wolke D, Cappuccio FP. Nonpharmacological treatments of insomnia for long-term painful conditions: a systematic review and meta-analysis of patient-reported outcomes in randomized controlled trials. Sleep. 2015; 38: 1751–1764.

[111] Baron KG, Reid KJ, Zee PC. Exercise to improve sleep in insomnia: exploration of the bidirectional effects. Journal of Clinical Sleep Medicine. 2013; 9: 819–824.

[112] Kaul M, Zee PC, Sahni AS. Effects of cannabinoids on sleep and their therapeutic potential for sleep disorders. Neurotherapeutics. 2021; 18: 217–227.

[113] Yin X, Gou M, Xu J, Dong B, Yin P, Masquelin F, et al. Efficacy and safety of acupuncture treatment on primary insomnia: a randomized controlled trial. Sleep Medicine. 2017; 37: 193–200.

[114] Suraev AS, Marshall NS, Vandrey R, McCartney D, Benson MJ, McGregor IS, et al. Cannabinoid therapies in the management of sleep disorders: a systematic review of preclinical and clinical studies. Sleep Medicine Reviews. 2020; 53: 101339.

[115] AminiLari M, Wang L, Neumark S, Adli T, Couban RJ, Giangregorio A, et al. Medical cannabis and cannabinoids for impaired sleep: a systematic review and meta-analysis of randomized clinical trials. Sleep. 2022; 45: zsab234.

[116] Wang L, Hong PJ, May C, Rehman Y, Oparin Y, Hong CJ, et al. Medical cannabis or cannabinoids for chronic non-cancer and cancer related pain: a systematic review and meta-analysis of randomised clinical trials. The BMJ. 2021; 374: n1034.

[117] Frange C, Naufel MF, Andersen ML, Ribeiro EB, Girão MJBC, Tufik S, et al. Impact of insomnia on pain in postmenopausal women. Climacteric. 2017; 20: 262–267.

[118] Meira E Cruz M, Lukic N, Wojczynska A, Steiger B, Guimarães AS, Ettlin DA. Insomnia in patients seeking care at an orofacial pain unit. Frontiers in Neurology. 2019; 10: 542.

[119] Sommer I, Lavigne G, Ettlin DA. Review of self-reported instruments that measure sleep dysfunction in patients suffering from temporomandibular disorders and/or orofacial pain. Sleep Medicine. 2015; 16: 27–38.

[120] Quartana PJ, Wickwire EM, Klick B, Grace E, Smith MT. Naturalistic changes in insomnia symptoms and pain in temporomandibular joint disorder: a cross-lagged panel analysis. Pain. 2010; 149: 325–331.

[121] Sanders AE, Akinkugbe AA, Bair E, Fillingim RB, Greenspan JD, Ohrbach R, et al. Subjective sleep quality deteriorates before development of painful temporomandibular disorder. The Journal of Pain. 2016; 17: 669–677.

[122] Dubrovsky B, Raphael KG, Lavigne GJ, Janal MN, Sirois DA, Wigren PE, et al. Polysomnographic investigation of sleep and respiratory parameters in women with temporomandibular pain disorders. Journal of Clinical Sleep Medicine. 2014; 10: 195–201.

[123] Maluly M, Dal Fabbro C, Andersen ML, Herrero Babiloni A, Lavigne GJ, Tufik S. Sleep bruxism and its associations with insomnia and OSA in the general population of Sao Paulo. Sleep Medicine. 2020; 75: 141–148.

[124] Adamo D, Sardella A, Varoni E, Lajolo C, Biasotto M, Ottaviani G, et al. The association between burning mouth syndrome and sleep disturbance: a case-control multicentre study. Oral Diseases. 2018; 24: 638–649.

[125] Tang NK, Goodchild CE, Salkovskis PM. Hybrid cognitive-behaviour therapy for individuals with insomnia and chronic pain: a pilot randomised controlled trial. Behaviour Research and Therapy. 2012; 50: 814–821.

[126] Herrero Babiloni A, Prie C, Dal Fabbro C, Harvey B, Schmittbuhl M, Desgroseilliers-Dussault E, et al. The effects of trazodone on sleep stability among patients with temporomandibular disorders: a brief report from an interrupted trial. Journal of Clinical Psychopharmacology. 2021; 41: 352–354.

[127] Gagnon Y, Mayer P, Morisson F, Rompré PH, Lavigne GJ. Aggravation of respiratory disturbances by the use of an occlusal splint in apneic patients: a pilot study. The International Journal of Prosthodontics. 2004; 17: 447–453.

[128] Nikolopoulou M, Ahlberg J, Visscher CM, Hamburger HL, Naeije M, Lobbezoo F. Effects of occlusal stabilization splints on obstructive sleep apnea: a randomized controlled trial. Journal of Orofacial Pain. 2013; 27: 199–205.

[129] Mayer P, Heinzer R, Lavigne G. Sleep bruxism in respiratory medicine practice. Chest. 2016; 149: 262–271.

[130] de Baat C, Verhoeff MC, Ahlberg J, Manfredini D, Winocur E, Zweers P, et al. Medications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism. Journal of Oral Rehabilitation. 2021; 48: 343–354.

[131] Fernández-de-Las-Peñas C, Fernández-Muñoz JJ, Palacios-Ceña M, Parás-Bravo P, Cigarán-Méndez M, Navarro-Pardo E. Sleep disturbances in tension-type headache and migraine. Therapeutic Advances in Neurological Disorders. 2017; 11: 1756285617745444.

[132] Cho SJ, Song TJ, Chu MK. Sleep and tension-type headache. Current Neurology and Neuroscience Reports. 2019; 19: 44.

[133] Yang CP, Wang SJ. Sleep in patients with chronic migraine. Current Pain and Headache Reports. 2017; 21: 39.

[134] Lucchesi LM, Hachul H, Yagihara F, Santos-Silva R, Tufik S, Bittencourt L. Does menopause influence nocturnal awakening with headache? Climacteric. 2013; 16: 362–368.

[135] Lavigne G, Khoury S, Chauny JM, Desautels A. Pain and sleep in post-concussion/mild traumatic brain injury. Pain. 2015; 156: S75–S85.

[136] Rains JC, Davis RE, Smitherman TA. Tension-type headache and sleep. Current Neurology and Neuroscience Reports. 2015; 15: 520.

[137] Vgontzas A, Pavlović JM. Sleep disorders and migraine: review of literature and potential pathophysiology mechanisms. Headache. 2018; 58: 1030–1039.

[138] Rains JC. Sleep and migraine: assessment and treatment of comorbid sleep disorders. Headache. 2018; 58: 1074–1091.

[139] Strother LC, Srikiatkhachorn A, Supronsinchai W. Targeted orexin and hypothalamic neuropeptides for migraine. Neurotherapeutics. 2018; 15: 377–390.

[140] Sarchielli P, Rainero I, Coppola F, Rossi C, Mancini M, Pinessi L, et al. Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine and medication-overuse headache: findings from cerebrospinal fluid. Cephalalgia. 2008; 28: 714–722.

[141] Holland PR, Goadsby PJ. Cluster headache, hypothalamus, and orexin. Current Pain and Headache Reports. 2009; 13: 147–154.

[142] Stanyer EC, Hoffmann J, Holland PR. Orexins and primary headaches: an overview of the neurobiology and clinical impact. Expert Review of Neurotherapeutics. 2024; 24: 487–496.

[143] Kaur S, Wang JL, Ferrari L, Thankachan S, Kroeger D, Venner A, et al. A genetically defined circuit for arousal from sleep during hypercapnia. Neuron. 2017; 96: 1153–1167.e5.

[144] Woods IG, Schoppik D, Shi VJ, Zimmerman S, Coleman HA, Greenwood J, et al. Neuropeptidergic signaling partitions arousal behaviors in zebrafish. The Journal of Neuroscience. 2014; 34: 3142–3160.

[145] Viticchi G, Di Stefano V, Altamura C, Falsetti L, Torrente A, Brunelli N, et al. Effects of prophylactic drug therapies and anti-calcitonin peptide-related monoclonal antibodies on subjective sleep quality: an Italian multicenter study. Sleep Medicine. 2024; 117: 87–94.

[146] Lee JH, Han K, Lee SY. Associations between obstructive sleep apnea and dental pain and chewing discomfort in Korean adults: a nationwide cross-sectional study. Scientific Reports. 2023; 13: 12768.

[147] Huang Z, Zhou N, Lobbezoo F, Almeida FR, Cistulli PA, Dieltjens M, et al. Dental sleep-related conditions and the role of oral healthcare providers: a scoping review. Sleep Medicine Reviews. 2023; 67: 101721.

[148] Apessos I, Lillis T, Voulgaris A, Archontogeorgis K, Steiropoulos P, Dabarakis N. Effect of third molar surgery on sleep health parameters of young adults: an observational study. Medicina. 2024; 60: 858.

[149] Magraw CB, Golden B, Phillips C, Tang DT, Munson J, Nelson BP, et al. Pain with pericoronitis affects quality of life. Journal of Oral and Maxillofacial Surgery. 2015; 73: 7–12.

[150] Heinzer R, Vat S, Marques-Vidal P, Marti-Soler H, Andries D, Tobback N, et al. Prevalence of sleep-disordered breathing in the general population: the HypnoLaus study. The Lancet. Respiratory Medicine. 2015; 3: 310–318.

[151] McArdle N, Reynolds AC, Hillman D, Moses E, Maddison K, Melton P, et al. Prevalence of common sleep disorders in a middle-aged community sample. Journal of Clinical Sleep Medicine. 2022; 18: 1503–1514.

[152] Costa YM, De Koninck BP, Elsaraj SM, Exposto FG, Herrero Babiloni A, Kapos FP, et al. Orofacial pain education in dentistry: a path to improving patient care and reducing the population burden of chronic pain. Journal of Dental Education. 2021; 85: 349–358.

[153] Kapos FP, Exposto FG, Oyarzo JF, Durham J. Temporomandibular disorders: a review of current concepts in aetiology, diagnosis and management. Oral Surgery. 2020; 13: 321–334.

[154] Farzin M, Taghva M, Babooie M. Comparison of temporomandibular disorders between menopausal and non-menopausal women. Journal of the Korean Association of Oral and Maxillofacial Surgeons. 2018; 44: 232–236.

[155] Galhardo APM, Mukai MK, Baracat MCP, da Fonseca AM, Roa CL, Sorpreso ICE, et al. Does temporomandibular disorder correlate with menopausal symptoms? Menopause. 2022; 29: 728–733.

[156] Dubrovsky B, Janal MN, Lavigne GJ, Sirois DA, Wigren PE, Nemelivsky L, et al. Depressive symptoms account for differences between self-reported versus polysomnographic assessment of sleep quality in women with myofascial TMD. Journal of Oral Rehabilitation. 2017; 44: 925–933.

[157] Bonsignore MR, Mazzuca E, Baiamonte P, Bouckaert B, Verbeke W, Pevernagie DA. REM sleep obstructive sleep apnoea. European Respiratory Review. 2024; 33: 230166.

[158] Karuga FF, Kaczmarski P, Białasiewicz P, Szmyd B, Jaromirska J, Grzybowski F, et al. REM-OSA as a tool to understand both the architecture of sleep and pathogenesis of sleep apnea-literature review. Journal of Clinical Medicine. 2023; 12: 5907.

[159] Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. American Journal of Epidemiology. 2013; 177: 1006–1014.

[160] Tufik S, Santos-Silva R, Taddei JA, Bittencourt LR. Obstructive sleep apnea syndrome in the Sao Paulo Epidemiologic Sleep Study. Sleep Medicine. 2010; 11: 441–446.

[161] Carberry JC, Amatoury J, Eckert DJ. Personalized management approach for OSA. Chest. 2018; 153: 744–755.

[162] Brown EC, Jugé L, Knapman FL, Burke PGR, Ngiam J, Sutherland K, et al. Mandibular advancement splint response is associated with the pterygomandibular raphe. Sleep. 2021; 44: zsaa222.

[163] Chiu HY, Chen PY, Chuang LP, Chen NH, Tu YK, Hsieh YJ, et al. Diagnostic accuracy of the Berlin questionnaire, STOP-BANG, STOP, and Epworth sleepiness scale in detecting obstructive sleep apnea: a bivariate meta-analysis. Sleep Medicine Reviews. 2017; 36: 57–70.

[164] Marti-Soler H, Hirotsu C, Marques-Vidal P, Vollenweider P, Waeber G, Preisig M, et al. The NoSAS score for screening of sleep-disordered breathing: a derivation and validation study. The Lancet. Respiratory Medicine. 2016; 4: 742–748.

[165] Laharnar N, Herberger S, Prochnow LK, Chen NH, Cistulli PA, Pack AI, et al. Simple and unbiased OSA prescreening: introduction of a new morphologic OSA prediction score. Nature and Science of Sleep. 2021; 13: 2039–2049.

[166] Punjabi NM. COUNTERPOINT: is the apnea-hypopnea index the best way to quantify the severity of sleep-disordered breathing? No. Chest. 2016; 149: 16–19.

[167] Heilbrunn ES, Ssentongo P, Chinchilli VM, Oh J, Ssentongo AE. Sudden death in individuals with obstructive sleep apnoea: a systematic review and meta-analysis. BMJ Open Respiratory Research. 2021; 8: e000656.

[168] Ong JC, Crawford MR, Dawson SC, Fogg LF, Turner AD, Wyatt JK, et al. A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia: main outcomes from the MATRICS study. Sleep. 2020; 43: zsaa041.

[169] Sweetman A, Lack L, Catcheside PG, Antic NA, Smith S, Chai-Coetzer CL, et al. Cognitive and behavioral therapy for insomnia increases the use of continuous positive airway pressure therapy in obstructive sleep apnea participants with comorbid insomnia: a randomized clinical trial. Sleep. 2019; 42: zsz178.

[170] Tu AY, Crawford MR, Dawson SC, Fogg LF, Turner AD, Wyatt JK, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. Journal of Clinical Sleep Medicine. 2022; 18: 789–800.

[171] Taranto-Montemurro L, Messineo L, Azarbarzin A, Vena D, Hess LB, Calianese NA, et al. Effects of the combination of atomoxetine and oxybutynin on OSA endotypic traits. Chest. 2020; 157: 1626–1636.

[172] Taranto-Montemurro L, Messineo L, Sands SA, Azarbarzin A, Marques M, Edwards BA, et al. The combination of atomoxetine and oxybutynin greatly reduces obstructive sleep apnea severity. A randomized, placebo-controlled, double-blind crossover trial. American Journal of Respiratory and Critical Care Medicine. 2019; 199: 1267–1276.

[173] Lavigne G, Herrero Babiloni A, Fabbro CD, Mayer P. Could atomoxetine-oxybutynin, a combination of medications being explored for OSA management, have any effect on sleep bruxism or jaw muscle tone? Chest. 2021; 159: 2117–2118.

[174] Carneiro-Barrera A, Díaz-Román A, Guillén-Riquelme A, Buela-Casal G. Weight loss and lifestyle interventions for obstructive sleep apnoea in adults: systematic review and meta-analysis. Obesity Reviews. 2019; 20: 750–762.

[175] Cistulli PA, Hedner J. Drug therapy for obstructive sleep apnea: from pump to pill? Sleep Medicine Reviews. 2019; 46: A1–A3.

[176] Wang L, Xu J, Zhan Y, Pei J. Acupuncture for obstructive sleep apnea (OSA) in adults: a systematic review and meta-analysis. BioMed Research International. 2020; 2020: 6972327.

[177] Carley DW, Prasad B, Reid KJ, Malkani R, Attarian H, Abbott SM, et al. Pharmacotherapy of apnea by cannabimimetic enhancement, the PACE clinical trial: effects of dronabinol in obstructive sleep apnea. Sleep. 2018; 41: zsx184.

[178] Ramar K, Rosen IM, Kirsch DB, Chervin RD, Carden KA, Aurora RN, et al.; American Academy of Sleep Medicine Board of Directors. Medical cannabis and the treatment of obstructive sleep apnea: an American academy of sleep medicine position statement. Journal of Clinical Sleep Medicine. 2018; 14: 679–681.

[179] Iftikhar IH, Bittencourt L, Youngstedt SD, Ayas N, Cistulli P, Schwab R, et al. Comparative efficacy of CPAP, MADs, exercise-training, and dietary weight loss for sleep apnea: a network meta-analysis. Sleep Medicine. 2017; 30: 7–14.

[180] Lin HY, Su PL, Lin CY, Hung CH. Models of anatomically based oropharyngeal rehabilitation with a multilevel approach for patients with obstructive sleep apnea: a meta-synthesis and meta-analysis. Sleep & Breathing. 2020; 24: 1279–1291.

[181] Srijithesh PR, Aghoram R, Goel A, Dhanya J. Positional therapy for obstructive sleep apnoea. Cochrane Database of Systematic Reviews. 2019; 5: CD010990.

[182] Dieltjens M, Vroegop AV, Verbruggen AE, Wouters K, Willemen M, De Backer WA, et al. A promising concept of combination therapy for positional obstructive sleep apnea. Sleep & Breathing. 2015; 19: 637–644.

[183] Camacho M, Chang ET, Neighbors CLP, Noller MW, Mack D, Capasso R, et al. Thirty-five alternatives to positive airway pressure therapy for obstructive sleep apnea: an overview of meta-analyses. Expert Review of Respiratory Medicine. 2018; 12: 919–929.

[184] Chang ET, Fernandez-Salvador C, Giambo J, Nesbitt B, Liu SY, Capasso R, et al. Tongue retaining devices for obstructive sleep apnea: a systematic review and meta-analysis. American Journal of Otolaryngology. 2017; 38: 272–278.

[185] Nguyen DK, Liang J, Durr M. Topical nasal treatment efficacy on adult obstructive sleep apnea severity: a systematic review and meta-analysis. International Forum of Allergy & Rhinology. 2021; 11: 153–161.

[186] Cheatle MD, Webster LR. Opioid therapy and sleep disorders: risks and mitigation strategies. Pain Medicine. 2015; 16: S22–S26.

[187] Mubashir T, Nagappa M, Esfahanian N, Botros J, Arif AA, Suen C, et al. Prevalence of sleep-disordered breathing in opioid users with chronic pain: a systematic review and meta-analysis. Journal of Clinical Sleep Medicine. 2020; 16: 961–969.

[188] Correa D, Farney RJ, Chung F, Prasad A, Lam D, Wong J. Chronic opioid use and central sleep apnea: a review of the prevalence, mechanisms, and perioperative considerations. Anesthesia and Analgesia. 2015; 120: 1273–1285.

[189] Tay DKL, Pang KP. Clinical phenotype of South-East Asian temporomandibular disorder patients with upper airway resistance syndrome. Journal of Oral Rehabilitation. 2018; 45: 25–33.

[190] Sanders AE, Essick GK, Fillingim R, Knott C, Ohrbach R, Greenspan JD, et al. Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort. Journal of Dental Research. 2013; 92: 70S–77S.

[191] Alessandri-Bonetti A, Scarano E, Fiorita A, Cordaro M, Gallenzi P. Prevalence of signs and symptoms of temporo-mandibular disorder in patients with sleep apnea. Sleep & Breathing. 2021; 25: 2001–2006.

[192] Wu JH, Lee KT, Kuo CY, Cheng CH, Chiu JY, Hung JY, et al. The association between temporomandibular disorder and sleep apnea—a nationwide population-based cohort study. International Journal of Environmental Research and Public Health. 2020; 17: 6311.

[193] Fransson AMC, Isacsson G, Nohlert E. The outcome of oral appliance therapy on position-dependent obstructive sleep apnea: a multicenter randomized controlled trial. American Journal of Orthodontics and Dentofacial Orthopedics. 2022; 162: 386–393.

[194] Nikolopoulou M, Aarab G, Ahlberg J, Hamburger HL, de Lange J, Lobbezoo F. Oral appliance therapy versus nasal continuous positive airway pressure in obstructive sleep apnea: a randomized, placebo-controlled trial on temporomandibular side-effects. Clinical and Experimental Dental Research. 2020; 6: 400–406.

[195] Alessandri-Bonetti A, Bortolotti F, Moreno-Hay I, Michelotti A, Cordaro M, Alessandri-Bonetti G, et al. Effects of mandibular advancement device for obstructive sleep apnea on temporomandibular disorders: a systematic review and meta-analysis. Sleep Medicine Reviews. 2019; 48: 101211.

[196] Almeida FR, Lowe AA, Otsuka R, Fastlicht S, Farbood M, Tsuiki S. Long-term sequellae of oral appliance therapy in obstructive sleep apnea patients: part 2. Study-model analysis. American Journal of Orthodontics and Dentofacial Orthopedics. 2006; 129: 205–213.

[197] Knappe SW, Bakke M, Svanholt P, Petersson A, Sonnesen L. Long-term side effects on the temporomandibular joints and oro-facial function in patients with obstructive sleep apnoea treated with a mandibular advancement device. Journal of Oral Rehabilitation. 2017; 44: 354–362.

[198] Li D, Lobbezoo F, Kuang B, Hilgevoord AAJ, de Vries N, Aarab G. Effects of continuous positive airway pressure and mandibular advancement appliance therapy on sleep bruxism in adults with obstructive sleep apnea: a pilot study. Sleep & Breathing. 2023; 27: 1857–1864.

[199] Martynowicz H, Wieczorek T, Macek P, Wojakowska A, Poręba R, Gać P, et al. The effect of continuous positive airway pressure and mandibular advancement device on sleep bruxism intensity in obstructive sleep apnea patients. Chronic Respiratory Disease. 2022; 19: 14799731211052301.

[200] Gauthier L, Laberge L, Beaudry M, Laforte M, Rompré PH, Lavigne GJ. Efficacy of two mandibular advancement appliances in the management of snoring and mild-moderate sleep apnea: a cross-over randomized study. Sleep Medicine. 2009; 10: 329–336.

[201] McCarthy K, Saripella A, Selvanathan J, Nagappa M, Englesakis M, Wang D, et al. Positive airway pressure therapy for chronic pain in patients with obstructive sleep apnea-a systematic review. Sleep & Breathing. 2022; 26: 47–55.

[202] Park JW, Mehta S, Fastlicht S, Lowe AA, Almeida FR. Changes in headache characteristics with oral appliance treatment for obstructive sleep apnea. Scientific Reports. 2021; 11: 2568.

[203] Sakamoto Y, Furuhashi A, Komori E, Ishiyama H, Hasebe D, Sato K, et al. The most effective amount of forward movement for oral appliances for obstructive sleep apnea: a systematic review. International Journal of Environmental Research and Public Health. 2019; 16: 3248.

[204] Pépin JL, Cistulli PA, Crespeigne E, Tamisier R, Bailly S, Bruwier A, et al. Mandibular jaw movement automated analysis for oral appliance monitoring in obstructive sleep apnea: a prospective cohort study. Annals of the American Thoracic Society. 2024; 21: 814–822.

[205] Franco L, Rompre PH, de Grandmont P, Abe S, Lavigne GJ. A mandibular advancement appliance reduces pain and rhythmic masticatory muscle activity in patients with morning headache. Journal of Orofacial Pain. 2011; 25: 240–249.

[206] Meira E Cruz M, Kryger MH, Morin CM, Palombini L, Salles C, Gozal D. Comorbid insomnia and sleep apnea: mechanisms and implications of an underrecognized and misinterpreted sleep disorder. Sleep Medicine. 2021; 84: 283–288.

[207] Meira E Cruz M. Comorbid insomnia and sleep apnea: COMISA. Dental clinics of North America. 2024; 68: 455–466.

[208] Luyster FS, Buysse DJ, Strollo PJ III. Comorbid insomnia and obstructive sleep apnea: challenges for clinical practice and research. Journal of Clinical Sleep Medicine. 2010; 6: 196–204.

[209] Luciano YM, Porcacchia AS, Tufik S, Andersen ML, Pires GN. Prevalence and incidence of co-morbid insomnia and sleep apnea (Comisa) in São Paulo, Brazil. Chest. 2024; 165: 1004–1008.

[210] Lechat B, Appleton S, Melaku YA, Hansen K, McEvoy RD, Adams R, et al. Comorbid insomnia and sleep apnoea is associated with all-cause mortality. The European Respiratory Journal. 2022; 60: 2101958.

[211] Sweetman A, Lack L, Crawford M, Wallace DM. Comorbid insomnia and sleep apnea: assessment and management approaches. Sleep Medicine Clinics. 2022; 17: 597–617.

[212] Meira e Cruz M, Santos I, Gozal D, Salles C, Rocha I, Ettlin D. Insomnia, sleep disordered breathing and cardiometabolic risk factors in patients complaining from pain in orofacial region. Sleep Medicine. 2022; 100: S82.

[213] Ferré S, García-Borreguero D, Allen RP, Earley CJ. New insights into the neurobiology of restless legs syndrome. Neuroscientist. 2019; 25: 113–125.

[214] Provini F, Chiaro G. Neuroimaging in restless legs syndrome. Sleep Medicine Clinics. 2015; 10: 215–26, xi.

[215] Winkelmann J, Schormair B, Xiong L, Dion PA, Rye DB, Rouleau GA. Genetics of restless legs syndrome. Sleep Medicine. 2017; 31: 18–22.

[216] El Gewely M, Welman M, Xiong L, Yin S, Catoire H, Rouleau G, et al. Reassessing GWAS findings for the shared genetic basis of insomnia and restless legs syndrome. Sleep. 2018; 41: zsy164.

[217] Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG. Genetics of restless legs syndrome: an update. Sleep Medicine Reviews. 2018; 39: 108–121.

[218] Winkelmann J, Allen RP, Högl B, Inoue Y, Oertel W, Salminen AV, et al. Treatment of restless legs syndrome: evidence-based review and implications for clinical practice (Revised 2017)§. Movement Disorders. 2018; 33: 1077–1091.

[219] Leung W, Singh I, McWilliams S, Stockler S, Ipsiroglu OS. Iron deficiency and sleep—a scoping review. Sleep Medicine Reviews. 2020; 51: 101274.

[220] Gossard TR, Trotti LM, Videnovic A, St Louis EK. Restless legs syndrome: contemporary diagnosis and treatment. Neurotherapeutics. 2021; 18: 140–155.

[221] Winkelman JW, Wipper B, Zackon J. Long-term safety, dose stability, and efficacy of opioids for patients with restless legs syndrome in the national RLS opioid registry. Neurology. 2023; 100: e1520–e1528.

[222] Rosen IM, Aurora RN, Kirsch DB, Carden KA, Malhotra RK, Ramar K, et al.; American Academy of Sleep Medicine Board of Directors. Chronic opioid therapy and sleep: an American academy of sleep medicine position statement. Journal of Clinical Sleep Medicine. 2019; 15: 1671–1673.

[223] Gottlieb DJ, Somers VK, Punjabi NM, Winkelman JW. Restless legs syndrome and cardiovascular disease: a research roadmap. Sleep Medicine. 2017; 31: 10–17.

[224] Kendzerska T, Kamra M, Murray BJ, Boulos MI. Incident cardiovascular events and death in individuals with restless legs syndrome or periodic limb movements in sleep: a systematic review. Sleep. 2017; 40: zsx013.

[225] Chiaro G, Manconi M. Restless legs syndrome, periodic limb movements during sleep and cardiovascular risk. Autonomic Neuroscience. 2019; 220: 102554.

[226] Hornyak M, Feige B, Riemann D, Voderholzer U. Periodic leg movements in sleep and periodic limb movement disorder: prevalence, clinical significance and treatment. Sleep Medicine Reviews. 2006; 10: 169–177.

[227] Drakatos P, Olaithe M, Verma D, Ilic K, Cash D, Fatima Y, et al. Periodic limb movements during sleep: a narrative review. Journal of Thoracic Disease. 2021; 13: 6476–6494.

[228] Benbir Senel G, Ozcelik EU, Karadeniz D. Cyclic alternating pattern analysis in periodic leg movements in sleep in patients with obstructive sleep apnea syndrome before and after positive airway pressure treatment. Journal of Clinical Neurophysiology. 2021; 38: 456–465.

[229] Aurora RN, Kristo DA, Bista SR, Rowley JA, Zak RS, Casey KR, et al.; American Academy of Sleep Medicine. The treatment of restless legs syndrome and periodic limb movement disorder in adults—an update for 2012: practice parameters with an evidence-based systematic review and meta-analyses: an American Academy of Sleep Medicine Clinical Practice Guideline. Sleep. 2012; 35: 1039–1062.

[230] Chung PW, Cho SJ, Kim WJ, Yang KI, Yun CH, Chu MK. Restless legs syndrome and tension-type headache: a population-based study. The Journal of Headache and Pain. 2017; 18: 47.

[231] van Oosterhout WP, van Someren EJ, Louter MA, Schoonman GG, Lammers GJ, Rijsman RM, et al. Restless legs syndrome in migraine patients: prevalence and severity. European Journal of Neurology. 2016; 23: 1110–1116.

[232] Schürks M, Winter A, Berger K, Kurth T. Migraine and restless legs syndrome: a systematic review. Cephalalgia. 2014; 34: 777–794.

[233] Grandner MA, Jackson NJ, Izci-Balserak B, Gallagher RA, Murray-Bachmann R, Williams NJ, et al. Social and behavioral determinants of perceived insufficient sleep. Frontiers in Neurology. 2015; 6: 112.

[234] Hanssen DJ, Naarding P, Collard RM, Comijs HC, Oude Voshaar RC. Physical, lifestyle, psychological, and social determinants of pain intensity, pain disability, and the number of pain locations in depressed older adults. Pain. 2014; 155: 2088–2096.

[235] Riley JL III, Gilbert GH, Heft MW. Socioeconomic and demographic disparities in symptoms of orofacial pain. Journal of Public Health Dentistry. 2003; 63: 166–173.

[236] de Sousa FS, Costa EM, Alves CMC, Queiroz RCDS, Tonello AS, Ribeiro CCC, et al. Socioeconomic inequalities and temporomandibular joint disorders in adolescents: contributions from a Maranhão cohort. Community Dental Health. 2021; 38: 192–197.

[237] Minervini G, Franco R, Marrapodi MM, Fiorillo L, Cervino G, Cicciù M. Economic inequalities and temporomandibular disorders: a systematic review with meta-analysis. Journal of Oral Rehabilitation. 2023; 50: 715–723.

[238] Saravanan A, Bajaj P, Mathews HL, Tell D, Starkweather A, Janusek L. Social support is inversely associated with sleep disturbance, inflammation, and pain severity in chronic low back pain. Nursing Research. 2021; 70: 425–432.

[239] Brooks Holliday S, Dubowitz T, Ghosh-Dastidar B, Beckman R, Buysse D, Hale L, et al. Do sleep and psychological distress mediate the association between neighborhood factors and pain? Pain Medicine. 2019; 20: 278–289.

[240] Charitos IA, Inchingolo AM, Ferrante L, Inchingolo F, Inchingolo AD, Castellaneta F, et al. The Gut Microbiota’s role in neurological, psychiatric, and neurodevelopmental disorders. Nutrients. 2024; 16: 4404.

[241] Lassmann Ł, Pollis M, Żółtowska A, Manfredini D. Gut bless your pain-roles of the gut microbiota, sleep, and melatonin in chronic orofacial pain and depression. Biomedicines. 2022; 10: 1528.

[242] Neroni B, Evangelisti M, Radocchia G, Di Nardo G, Pantanella F, Villa MP, et al. Relationship between sleep disorders and gut dysbiosis: what affects what? Sleep Medicine. 2021; 87: 1–7.

[243] Li Y, Hao Y, Fan F, Zhang B. The role of microbiome in insomnia, circadian disturbance and depression. Frontiers in Psychiatry. 2018; 9: 669.

[244] Wankhede NL, Kale MB, Kyada A, M RM, Chaudhary K, Naidu KS, et al. Sleep deprivation-induced shifts in gut microbiota: implications for neurological disorders. Neuroscience. 2025; 565: 99–116.

[245] Minerbi A, Gonzalez E, Brereton NJB, Anjarkouchian A, Dewar K, Fitzcharles MA, et al. Altered microbiome composition in individuals with fibromyalgia. Pain. 2019; 160: 2589–2602.

[246] González-Álvarez ME, Riquelme-Aguado V, González-Pérez Á, Murillo-Llergo R, Manjón-Olmedillas M, Turroni S, et al. Association between systemic neuroinflammation, pain perception and clinical status in fibromyalgia patients: cross-sectional study. Cells. 2024; 13: 1719.

[247] Wu J, Zhang B, Zhou S, Huang Z, Xu Y, Lu X, et al. Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study. Frontiers in Microbiology. 2023; 14: 1236847.

[248] Li Q, Xu T, Shao C, Gao W, Wang M, Dong Y, et al. Obstructive sleep apnea is related to alterations in fecal microbiome and impaired intestinal barrier function. Scientific Reports. 2023; 13: 778.

[249] Huang X, Chen X, Gong X, Xu Y, Xu Z, Gao X. Characteristics of salivary microbiota in children with obstructive sleep apnea: a prospective study with polysomnography. Frontiers in Cellular and Infection Microbiology. 2022; 12: 945284.

[250] Wang PP, Wang LJ, Fan YQ, Dou ZJ, Han JX, Wang B. Analysis of the characteristics of intestinal microbiota in patients with different severity of obstructive sleep apnea. Scientific Reports. 2024; 14: 21552.

[251] Fan C, Guo L, Gu H, Huo Y, Lin H. Alterations in oral-nasal-pharyngeal microbiota and salivary proteins in mouth-breathing children. Frontiers in Microbiology. 2020; 11: 575550.

[252] Erdrich S, Hawrelak JA, Myers SP, Harnett JE. Determining the association between fibromyalgia, the gut microbiome and its biomarkers: a systematic review. BMC Musculoskeletal Disorders. 2020; 21: 181.

[253] Tao R, Liu S, Crawford J, Tao F. Gut-brain crosstalk and the central mechanisms of orofacial pain. Brain sciences. 2023; 13: 1456.

[254] Forsythe P, Bienenstock J, Kunze WA. Vagal pathways for microbiome-brain-gut axis communication. Advances in Experimental Medicine and biology. 2014; 817: 115–133.

[255] Ju HM, Ahn YW, Ok SM, Jeong SH, Na HS, Chung J. Distinctive salivary oral microbiome in patients with burning mouth syndrome depending on pain intensity compared to healthy subjects. Journal of Dental Sciences. 2025; 20: 462–469.

[256] Ma Y, Liu S, Shu H, Crawford J, Xing Y, Tao F. Resveratrol alleviates temporomandibular joint inflammatory pain by recovering disturbed gut microbiota. Brain, Behavior, and Immunity. 2020; 87: 455–464.

[257] Tofani GSS, Leigh SJ, Gheorghe CE, Bastiaanssen TFS, Wilmes L, Sen P, et al. Gut microbiota regulates stress responsivity via the circadian system. Cell Metabolism. 2025; 37: 138–153.e5.

[258] Henssen DJHA, Derks B, van Doorn M, Verhoogt NC, Staats P, Vissers K, et al. Visualizing the trigeminovagal complex in the human medulla by combining ex-vivo ultra-high resolution structural MRI and polarized light imaging microscopy. Scientific Reports. 2019; 9: 11305.

[259] Möller M, Mehnert J, Schroeder CF, May A. Noninvasive vagus nerve stimulation and the trigeminal autonomic reflex: an fMRI study. Neurology. 2020; 94: e1085–e1093.

[260] Möller M, Schroeder CF, May A. Vagus nerve stimulation modulates the cranial trigeminal autonomic reflex. Annals of Neurology. 2018; 84: 886–892.

[261] Prott LS, Spitznagel FA, Hugger A, Langner R, Gierthmühlen PC, Gierthmühlen M. Transcutaneous auricular vagus nerve stimulation for the treatment of myoarthropatic symptoms in patients with craniomandibular dysfunction—a protocol for a randomized and controlled pilot trial. Pilot and Feasibility Studies. 2024; 10: 27.

[262] Greenspan JD, Slade GD, Bair E, Dubner R, Fillingim RB, Ohrbach R, et al. Pain sensitivity and autonomic factors associated with development of TMD: the OPPERA prospective cohort study. The Journal of Pain. 2013; 14: T63–T74.e1–e6.

[263] International Classification of Orofacial Pain, 1st edition (ICOP). Cephalalgia. 2020; 40: 129–221.

[264] Morin CM, Benca R. Chronic insomnia. The Lancet. 2012; 379: 1129–1141.

[265] Dissanayake HU, Bin YS, Ucak S, de Chazal P, Sutherland K, Cistulli PA. Association between autonomic function and obstructive sleep apnea: a systematic review. Sleep Medicine Reviews. 2021; 57: 101470.

[266] Dissanayake HU, Bin YS, Sutherland K, Ucak S, de Chazal P, Cistulli PA. The effect of obstructive sleep apnea therapy on cardiovascular autonomic function: a systematic review and meta-analysis. Sleep. 2022; 45: zsac210.

[267] Gigandet MB, Radtke RA. Teaching neuroimage: obstructive sleep apnea induced by a vagal nerve stimulator. Neurology. 2024; 103: e209847.

[268] Solow B, Ovesen J, Nielsen PW, Wildschiødtz G, Tallgren A. Head posture in obstructive sleep apnoea. European Journal of Orthodontics. 1993; 15: 107–114.

[269] Sökücü O, Okşayan R, Uyar M, Ademci KE, Üşümez S. Relationship between head posture and the severity of obstructive sleep apnea. American Journal of Orthodontics and Dentofacial Orthopedics. 2016; 150: 945–949.

[270] Piccin CF, Pozzebon D, Scapini F, Corrêa EC. Craniocervical posture in patients with obstructive sleep apnea. International Archives of Otorhinolaryngology. 2016; 20: 189–195.

[271] Mahmoud NF, Hassan KA, Abdelmajeed SF, Moustafa IM, Silva AG. The relationship between forward head posture and neck pain: a systematic review and meta-analysis. Current reviews in Musculoskeletal Medicine. 2019; 12: 562–577.

[272] Wang X, Zhou T, Huang W, Zhang J, Zou J, Guan J, et al. Differences in physiologic endotypes between nonpositional and positional OSA: results from the shanghai sleep health study cohort. Chest. 2024; 166: 212–225.

[273] Park JS, Kim YB, Park IS, Han SA, Kang SH, Lee KC, et al. Polysomnographic phenotype of positional obstructive sleep apnea. Journal of Rhinology. 2024; 31: 168–175.

[274] Miettinen T, Mäntyselkä P, Hagelberg N, Mustola S, Kalso E, Lötsch J. Machine learning suggests sleep as a core factor in chronic pain. Pain. 2021; 162: 109–123.

[275] Yang S, Bie X, Wang Y, Li J, Wang Y, Sun X. Image features of resting-state functional magnetic resonance imaging in evaluating poor emotion and sleep quality in patients with chronic pain under artificial intelligence algorithm. Contrast Media & Molecular Imaging. 2022; 2022: 5002754.