Potential Role of Obstructive Sleep Apnea on Pain Sensitization and Jaw Function in Temporomandibular Disorder Patients

Jeong-Hyun Kang; Hyun Jun Kim

doi:10.3346/jkms.2022.37.e307

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Kang and Kim: Potential Role of Obstructive Sleep Apnea on Pain Sensitization and Jaw Function in Temporomandibular Disorder Patients

Original Article

Dentistry

Journal of Korean Medical Science 2022; 37(39): e307.

Published online: 6 October 2022

DOI: https://doi.org/10.3346/jkms.2022.37.e307

Potential Role of Obstructive Sleep Apnea on Pain Sensitization and Jaw Function in Temporomandibular Disorder Patients

Jeong-Hyun Kang¹

, Hyun Jun Kim²

¹Clinic of Oral Medicine and Orofacial Pain, Institute of Oral Health Science, Ajou University School of Medicine, Suwon, Korea.

²Department of Otolaryngology, School of Medicine, Ajou University, Suwon, Korea.

Address for Correspondence: Hyun Jun Kim, MD, PhD. Department of Otolaryngology, School of Medicine, Ajou University, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea. entkhj@ajou.ac.kr

Received 20 September 2022 Accepted 28 September 2022

The Korean Academy of Medical Sciences

https://creativecommons.org/licenses/by-nc/4.0/

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The relationships between obstructive sleep apnea (OSA) and diverse types of pain disorders have been reported. However, the interaction between OSA and pain-related temporomandibular disorder (TMD) remains obscure.

Methods

A total of 60 adults (male/female, 48/12; mean age, 41.7 ± 13.2 years) with pain-related TMD were enrolled. All participants underwent overnight full-channel polysomnography and had assessment of size and position of the tongue, tonsillar size, height, and weight. Diagnostic Criteria/TMD criteria was applied to diagnose TMD. Myofascial trigger points (TrPs) were bilaterally evaluated in the two masticatory and four cervical muscles including the temporalis, masseter, trapezius, sternocleidomastoid, occipitalis, and splenius capitis muscles. Participants were divided into three groups in accordance with their levels of OSA.

Results

The significantly higher number of active TrPs were detected in participants with severe OSA. The number of active TrPs in the masticatory muscles significantly interacted with diverse types of apneic and arousal indices.

Conclusion

The myofascial pain modulating mechanisms and jaw function could have interactions with nocturnal hypoxia and sleep fragmentation in chronic pain-related TMD patients.

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Graphical Abstract

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Keywords: Obstructive Sleep Apnea, Temporomandibular Disorder, Oxygen Saturation, Pain, Trigger Point, Sleep Fragmentation

INTRODUCTION

Obstructive sleep apnea (OSA), affecting 9% - 49% of the general population,1 2 is featured by intermittent complete or partial collapse of the upper airway structures during sleep, resulting in airflow pausing or reduction.3 OSA is accompanied by sleep fragmentation and nocturnal hypoxemia which can inevitably lead to a variety of comorbidities and their sequelae.4 Many previous studies have focused on the consequences of untreated OSA such as cardiovascular diseases, cognitive impairment, and increase risk of mortality.5 6 7 8 9 Therefore, prompt diagnosis and management of OSA is critical for reducing the possibilities of developing its comorbidities.

A bidirectional link between poor sleep quality and a variety of pain conditions, particularly musculoskeletal pain disorders has been proposed.10 11 12 13 14 15 The relationship between OSA and systemic inflammation appears to have an impact on the development and aggravation of pain symptoms.16 Hypoxemia in OSA has been proven to increase the expression of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor-α and overexpression of opioid receptors 16 17 both of which influence central and peripheral pain sensitization and pain amplification mechanisms.16 18 19 The relationship between sleep fragmentation and pain sensitization have been proposed, also.11 20 21 Pain management in OSA patient is complex owing to complicated pain mechanisms and pathophysiology of OSA, therefore the clear management guidelines or treatment protocol have not been proposed yet.

Temporomandibular disorder (TMD) is a collective term referring pain conditions and functional jaw disabilities occurring in the masticatory muscles, temporomandibular joints, and their related structures.22 Several previous studies have emphasized the relationships between sleep disorders and TMD.10 11 13 18 19 23 24 Approximately, 36% of TMD cases met insomnia diagnostic criteria and over 28% met criteria for OSA.18 Otherwise, 51% of OSA patients had TMD signs and symptoms compared to normal controls.10 In addition, one long term cohort study suggested OSA as a risk factor for the development of first onset TMD.19 The effects of hypoxemia and sleep fragmentation owing to oxygen desaturation and respiratory arousal during night on peripheral and central sensitization in other pain conditions have been postulated from previous reports, however, the clear interactions among oxygen desaturation, sleep fragmentation, and pain-related TMD has not been elucidated, so far. Hence, the aim of the present study was to clarify the potential role of OSA on severity of orofacial pain and jaw function in patients with chronic pain-related TMD using polysomnography (PSG) data.

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METHODS

Participants and procedure

This was a cross-sectional study, conducted using the clinical records of TMD and PSG data from 60 adults (male/female, 48/12; mean age, 41.7 ± 13.2 years; age range, 19–74 years) who had been referred to the department of dentistry at a tertiary university hospital, owing to chronic orofacial pain and/or sleep disturbance at night. For more than six months, all participants experienced pain-related TMD. Participants with neurodegenerative disorders, fibromyalgia, chronic fatigue syndrome, craniofacial anomalies, regular use of analgesic and psychotic medications, history of botulinum toxin injection in the masticatory and cervical muscles within 6 months of study entry, and communication incapability were all excluded.

The participants were divided into three groups accordance with the level of OSA. Participants in the control group did not have OSA, whereas those in the mild-moderate and severe OSA group did. All participants underwent assessment of height, weight, size and position of the tongue, and tonsillar size by a trained technician. To evaluate the size and position of the tongue, the modified Mallampati’s score was applied25 and tonsillar size were determined using a grading system proposed in a previous report.26 Two self-administered sleep questionnaires, the Pittsburgh sleep quality index (PSQI) and the Epworth sleep index (ESS) were used to determine the subjective sleep quality and daytime sleepiness, respectively.

Polysomnography

All participants underwent a full overnight in-laboratory PSG (Embla N 7000, ResMed, Germany). The following variables were assessed; total sleep time, sleep latency, sleep efficiency, rapid eye movement (REM) latency, wake after sleep onset (WASO), apnea-hypopnea index (AHI), respiratory disturbance index (RDI), respiratory effort related arousal, oxygen desaturation index, arousal indices, and degree of oxygen saturation. Sleep montages for electroencephalography, electromyogram, nasal airflow using a pressure cannula, oral airflow using a thermistor, snoring recorded using a microphone attached near the thyroid cartilage, respiratory thoracic and abdominal effort measured using plethysmography belts, transthoracic two-lead electrocardiogram, and pulse oximetry were all determined.

Diagnosis of OSA

OSA was determined on the basis of the definition per Center for Medicare and Medicaid Services.27 The diagnosis requires the observed apnea and hypopnea coupled with an AHI of higher than five. The AHI was calculated as the sum of obstructive and mixed apneas and hypopneas per hour of sleep as defined by the American academy of sleep medicine scoring manual.27 28 All of the participants were divided into three groups. Participants with AHIs less than or equal to 5 were classified as normal controls, those with AHIs between 5 and 30 were classified as the mild-moderate OSA group, and those with AHI greater than 30 were determined as severe OSA group.29

Diagnosis of the TMD and determination of the number of myofascial trigger points (TrPs) in the masticatory and cervical muscles

TMD was diagnosed according to the Diagnostic Criteria for/TMD (DC/TMD) criteria. Clinical parameters, including amount of pain free opening and maximum unassisted opening, as well as the duration of pain-related TMD symptoms, such as difficulties in opening and/or closing the mouth, and pain in the temple, jaw, and preauricular areas were evaluated. The subjective severity of chronic orofacial pain was assessed using a visual analogue scale and Global Chronic Pain Scale (GCPS) in accordance with the DC/TMD axis II. GCPS is a reliable and valid instrument which assess pain intensity and pain related disability including two subscales, pain intensity and pain disability. Myofascial TrPs were measured bilaterally in the two masticatory and four cervical muscles including the temporalis, masseter, trapezius, sternocleidomastoid, occipitalis, and splenius capitis muscles. TrPs were determined on the basis of the criteria suggested by Simon and Travell.30 The parameters associated with TMD and the number of TrPs in the masticatory and cervical muscles were assessed by one orofacial pain specialist (JHK).

Statistical analysis

A total sample size of 60 participants in a two-way analysis of variance (ANOVA) provided a statistical power of 88.1% at a 0.05 significance level with an effect size of 0.4, according to the power analysis. The data were found to be normally distributed using the Shapiro-Wilk normality test, hence parametric analysis was applied. To compare the participants’ demographic characteristics, PSG results, and parameters related to TMD of the participants, one-way ANOVA and chi-square test were used for continuous and categorical variables, respectively.

Pearson’s correlation coefficient was applied to determine the associations between results from PSG and parameters about pain-related TMD. The variables related with PSG which showed significant differences among the groups were adopted in the correlation analysis. All tests were two-sided and P values which were less than 0.05 by one-way ANOVA and χ² test, and less than 0.0005 by Pearson’s correlation analysis with Bonferroni’s correction, were considered statistically significant, respectively.

Ethics statement

The research protocol was approved by the Institutional Review Board of the Ajou university hospital (AJIRB-DB-2022-369) and the institutional review board waived the documentation of informed consent due to the retrospective design of the study.

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RESULTS

Demographic characteristics, subjective sleep quality, and TMD features of participants

There were no statistically significant differences of the age, sex distribution, size and position of the tongue and tonsil among the three groups. On the other hand, differences in body mass index (P = 0.007), ESS (P < 0.001), and PSQI (P = 0.015) showed statistical significance. The parameters related with pain-related TMD symptoms did not show significant differences among three groups except the number of active TrPs in the masticatory muscles and extent of chronicity of the pain-related TMD (P = 0.045) (Table 1).

Table 1

Comparison of demographic characteristics, subjective sleep quality, and TMD features of participants

Variables	Control (n = 20)	Mild-Moderate (n = 19)	Severe (n = 21)	P value	Post hoc
Age, yr	38.5 ± 9.4	41.4 ± 15.8	45.0 ± 13.5	0.289
Sex (mMale/female)^a	13/7	16/3	19/2	0.107
BMI	25.4 ± 3.8	27.7 ± 3.6	29.3 ± 3.8	0.007^*	Control-severe
ESS	12.3 ± 3.7	7.52 ± 3.34	10.4 ± 4.3	< 0.001^**	Control-mild-moderate
PSQI	9.50 ± 3.00	6.95 ± 2.53	7.90 ± 2.53	0.015^*	Control-mild-moderate
Tonsillar size^a	2 (1–2)	2 (1–3)	2 (2–2.5)	0.398
Modified Mallampati score^a	3 (2.25–4)	3 (3–3)	3 (3–4)	0.308
VAS	4.05 ± 2.78	5.21 ± 3.15	4.81 ± 2.42	0.422
Duration of painful TMD symptoms, mon	34.0 ± 46.5	27.9 ± 36.7	56.2 ± 59.3	0.160
Pain free opening, mm	46.4 ± 8.8	47.4 ± 8.4	42.9 ± 10.4	0.280
Maximum unassisted opening, mm	48.3 ± 5.7	49.0 ± 7.9	46.0 ± 10.1	0.493
Number of active TrPs in masticatory muscles	0.65 ± 0.93	0.79 ± 0.85	1.71 ± 1.23	0.003^*	Control-severe
Number of active TrPs in cervical muscles	0.75 ± 2.31	0.26 ± 0.93	0.62 ± 1.91	0.693
Number of latent TrPs in masticatory muscles	0.85 ± 0.81	0.47 ± 0.61	0.38 ± 0.74	0.104
Number of latent TrPs in cervical muscles	0.35 ± 0.88	0.26 ± 0.93	0.33 ± 1.32	0.964
Number of positive sites of capsule palpation	0.75 ± 0.64	0.63 ± 0.50	0.71 ± 0.64	0.820
GCPS^a	1 (1–2)	1 (1–3)	3 (1.5–3)	0.045^*

TMD = temporomandibular disorders, BMI = body mass index, ESS = Epworth sleep index, GCPS = graded chronic pain scale, PSQI = Pittsburgh sleep quality index, OSA = obstructive sleep apnea, =,TrP = trigger point, VAS = visual analog scale.

Descriptive values are shown as mean ± SD or median (25^th–75^th percentile). Data obtained from one-way ANOVA. Post-hoc analysis was conducted by Bonferroni’s test.

^aData obtained from χ² test.

^*P < 0.05, ^**P < 0.001 by one-way ANOVA and χ² test.

The distribution of DC/TMD diagnosis including intra-articular TMD and presence of degenerative joint disease and headache attributed to TMD did not show statistical significance among groups, however distribution of pain-related TMD diagnosis showed significant differences (P < 0.001) among the groups. The participants with severe OSA presented higher prevalence of myofascial pain compared to other two groups (Table 2).

Table 2

Diagnostic classification based on the DC/TMD criteria

Diagnostic classification	Control (n = 20)	Mild-moderate (n = 19)	Severe (n = 21)	P value
Normal disc/DD with reduction/DD with reduction with intermittent locking/DD w/o reduction with limited opening/DD w/o reduction without limited opening/subluxation^a	12/18/1/3/4/2	9/19/1/1/5/3	18/10/1/3/5/5	0.194
None/myalgia/MFP/arthralgia/myalgia+arthralgia/myofascial pain+arthraltia^a	4/15/7/7/3/4	13/6/9/2/4/4	4/3/24/1/4/6	< 0.001^**
Degenerative joint disease^a	39/1	33/5	38/4	0.221
Headache attributed to TMD	16/4	17/2	15/6	0.131

Data obtained from χ² test.

DD = disc displacement, TMD = temporomandibular disorders, TMJ = temporomandibular joint MFP = myofascial pain.

^aThe diagnosis of intra-articular TMD, pain-related TMD, and presence of degenerative joint diseases were conducted separately in both sides of the TMJs.

^*P < 0.05, ^**P < 0.001 by χ² test.

PSG results

The length of REM sleep (P = 0.041) and non-REM (NREM) stage 1 (P < 0.001) and 3 sleep (P = 0.013) showed statistical differences among the groups. Moreover, differences of AHI (P < 0.001), RDI (P < 0.001), total arousal (P < 0.001), mean (P < 0.001) and lowest oxygen saturation (P < 0.001), and average oxygen desaturation (P < 0.001) showed statistical significance (Table 3).

Table 3

Polysomnography results of the participants

Variables		Control (n = 20)	Mild-moderate (n = 19)	Severe (n = 21)	P value	Post hoc
Total sleep time, min		376.3 ± 58.6	381.7 ± 51.3	372.9 ± 63.3	0.891
	N1 (%)	11.7 ± 4.9	13.5 ± 7.5	26.8 ± 13.2	< 0.001^**	Control-severe
	N1 (%)	11.7 ± 4.9	13.5 ± 7.5	26.8 ± 13.2	< 0.001^**	Mild-moderate-severe
	N2 (%)	59.9 ± 9.2	61.0 ± 8.4	54.2 ± 12.4	0.083
	N3 (%)	9.81 ± 7.91	4.56 ± 7.42	2.84 ± 7.31	0.013^*	Control-severe
	REM (%)	18.7 ± 5.4	21.0 ± 5.9	16.2 ± 6.0	0.041^*	Mild-moderate-severe
Sleep latency, min		34.4 ± 91.1	17.2 ± 17.4	17.1 ± 21.4	0.522
Sleep efficiency (%)		81.0 ± 17.7	82.8 ± 11.4	81.0 ± 12.3	0.888
REM latency, min		134.0 ± 58.0	116.5 ± 56.3	116.7 ± 74.4	0.613
Wake after sleep onset, min		62.9 ± 48.9	62.3 ± 55.5	68.2 ± 54.0	0.925
AHI		3.69 ± 2.66	17.8 ± 5.0	51.9 ± 20.0	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Obstructive apnea	0.65 ± 1.35	3.17 ± 3.03	22.3 ± 15.4	< 0.001^**	Control-severe
	Central apnea	0.42 ± 0.66	0.48 ± 0.60	1.45 ± 1.64	0.005^*	Control-severe
	Central apnea	0.42 ± 0.66	0.48 ± 0.60	1.45 ± 1.64	0.005^*	Mild-moderate-severe
	Mixed apnea	0.06 ± 0.11	0.74 ± 2.50	7.80 ± 11.6	< 0.001^**	Control-severe
	Hypopnea	2.49 ± 2.12	13.4 ± 4.9	22.6 ± 13.7	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Supine AHI	3.39 ± 3.20	19.8 ± 10.5	56.7 ± 21.4	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
RDI		11.0 ± 5.3	26.1 ± 5.8	57.0 ± 17.6	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
ODI		3.07 ± 2.24	17.1 ± 4.86	50.0 ± 19.2	0.213
Relative snoring time (%)		28.0 ± 20.1	36.4 ± 22.8	47.0 ± 19.1	0.017^*	Control-severe
PLMI		4.33 ± 9.20	1.39 ± 5.35	1.54 ± 5.61	0.331
Arousal
	Total arousal	18.3 ± 6.8	20.6 ± 7.6	47.3 ± 18.4	< 0.001^**	Control-severe
	Total arousal	18.3 ± 6.8	20.6 ± 7.6	47.3 ± 18.4	< 0.001^**	Mild-moderate-severe
	RERA	7.29 ± 4.22	8.17 ± 4.68	5.56 ± 5.21	0.213
	Respiratory arousal	1.99 ± 1.95	9.12 ± 4.54	40.4 ± 20.4	< 0.001^**	Control-severe
	Spontaneous arousal	8.50 ± 4.53	3.31 ± 2.33	4.63 ± 15.6	0.225
	PLM arousal	0.50 ± 1.34	0	0.10 ± 0.41	0.135
Oxygen saturation
	Mean oxygen saturation	97.1 ± 0.5	95.2 ± 1.14	93.1 ± 2.5	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Lowest oxygen saturation	90.6 ± 3.7	82.6 ± 8.9	74.8 ± 9.0	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Average oxygen desaturation	3.62 ± 1.02	5.17 ± 2.27	8.98 ± 4.40	< 0.001^**	Control-severe
	Average oxygen desaturation	3.62 ± 1.02	5.17 ± 2.27	8.98 ± 4.40	< 0.001^**	Mild-moderate-severe
	Average oxygen saturation during wake	97.3 ± 0.5	95.9 ± 1.0	94.5 ± 1.8	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Average oxygen saturation during REM	91.2 ± 0.7	94.8 ± 1.8	92.2 ± 3.5	< 0.001^**	Control-mild-moderate
						Control-severe
						Mild-moderate-severe
	Average oxygen saturation during NREM	97.0 ± 0.6	95.4 ± 1.1	88.7 ± 20.5	0.077

Descriptive values are shown as mean ± SD.

Data obtained from one-way ANOVA. Post-hoc analysis was conducted by Bonferroni’s test.

N1 = NREM stage 1, N2 = NREM stage 2, N3 = NREM stage 3, REM = rapid eye movement, AHI = apnea-hypopnea index, RDI = respiratory disturbance index, ODI = oxygen desaturation index, PLMI = periodic limb movement index, RERA = respiratory effort-related arousal, PLM = periodic limb movement, NREM = non-REM.

^*P < 0.05, ^**P < 0.001 by one-way ANOVA.

Associations among variables related with pain-related TMD and sleep apnea

The number of active TrPs in the masticatory muscles showed significant interactions with variety of apneic and arousals indices including AHI, RDI, respiratory arousal, and degree of mean oxygen saturation, average oxygen desaturation, and average oxygen saturation during REM sleep. The degree of the pain free opening and maximum unassisted opening did not present significant correlation with parameters related with sleep quality and oxygen desaturations (Table 4).

Table 4

Correlations between TMD pain parameters and sleep characteristics

Variables		Duration of TMD symptoms	VAS	Number of active TrPs in masticatory muscles	Pain free opening	Maximum unassisted opening
ESS		0.040	0.130	−0.128	−0.048	−0.001
PSQI		−0.104	0.300	−0.045	−0.161	−0.135
N1		0.068	−0.152	0.197	0.005	−0.006
N2		−0.075	0.092	−0.063	−0.150	−0.051
N3		−0.086	0.126	−0.139	0.277	0.231
R		0.116	−0.037	−0.081	−0.118	−0.185
AHI		0.129	0.066	0.485^*	−0.186	−0.20
	Obstructive apnea	0.117	−0.044	0.334^*	−0.225	−0.277
	Central apnea	−0.054	−0.060	0.217	−0.046	−0.064
	Mixed apnea	−0.101	−0.136	0.252	−0.046	−0.079
	Hypopnea	0.221	0.332^*	0.337^*	−0.088	−0.070
RDI		0.136	0.076	0.436^*	−0.182	−0.184
Relative snoring time		0.176	0.289	0.234	−0.050	0.018
Arousal
	Total arousal	0.117	−0.155	0.241	−0.130	−0.193
	Respiratory arousal	0.115	−0.073	0.353^*	−0.170	−0.234
Oxygen saturation
	Mean oxygen saturation	−0.001	−0.050	−0.412^*	0.077	0.119
	Lowest oxygen saturation	0.033	−0.109	−0.495^**	0.204	0.281
	Average oxygen desaturation	0.007	−0.058	0.392^*	−0.186	−0.218
	Average oxygen saturation during wake	−0.110	−0.082	−0.393^*	0.088	0.133
	Average oxygen saturation during REM	−0.005	−0.096	−0.388^*	0.151	0.214

The figures in bold indicate values with statistical significance.

TMD = temporomandibular disorders, VAS = visual analog scale, TrP = trigger point, ESS = Epworth sleep index, PSQI = Pittsburgh sleep quality index, N1 = NREM stage 1, N2 = NREM stage 2, N3 = NREM stage 3, AHI = apnea-hypopnea index, RDI = respiratory disturbance index, REM = rapid eye movement sleep, NREM = non-REM.

^*P < 0.0005, ^**P < 0.00001 by Pearson’s correlation analysis with Bonferroni’s correction.

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DISCUSSION

OSA is a chronic condition which is often associated with diverse types of comorbidities including cardiovascular disease and cognitive impairment, increasing the risk of mortality.5 6 7 OSA also has an effect on pain modulating mechanism in diverse types of pain disorders.11 18 31 32 33 34 35 TMD, one of the most common musculoskeletal disorders in the general population appears to interact with sleep disorders including OSA10 11 13 18 19 23 but the underlying mechanisms have not been revealed. The purpose of the current study was to elucidate the potential relationships among OSA, orofacial pain, and jaw function in patients with chronic pain-related TMD.

The novel findings of the present study were the significant correlations between the number of active TrPs in the masticatory muscles and the degree of oxygen desaturation. The association between higher analgesic sensitivity to opioid and nocturnal oxygen desaturation in OSA patients have been observed, previously.17 Nocturnal oxygen desaturation appeared to play a role in upregulation of pro-inflammatory cytokine levels, particularly, interleukin-6 which can influence on occurrence of hyperalgesia through enhancement of transient receptor potential vanilloid 1 activity.36 37 Moreover, there has been some evidence that interleukin-6 may induce enhancement of N-methy-D-aspartate receptor activity which may lead to impaired descending pain inhibitory pathways.38 39 Therefore, the nocturnal hypoxic condition in pain-related TMD patients may have associations with increased pain sensitivity and altered descending pain inhibitory pathway and finally this can have influence on development of central sensitization and hypersensitive taut bands in the masticatory muscles.

Several previous reports have proposed the relationship between sleep fragmentation and pain sensitization.11 20 21 Aforementioned results also supported this phenomenon that respiratory arousals had significant correlations with the number of active TrPs in the masticatory muscles. Sleep deprivation can cause myalgia, tenderness, and chronic fatigue and one study suggested that sleep deprivation impairs descending pain-inhibition pathways that are crucial for controlling and coping with pain.21 Slow wave NREM sleep seems to have a role in suppression of cortisol activity in feedback loop of the hypothalamus-pituitary-adrenal (HPA) axis.40 The chronic TMD patients presented altered feedback mechanisms of HPA axis and increased the levels of orofacial pain intensity and pain-related jaw function disability.41 Hence, disrupted slow wave sleep and sleep fragmentation owing to apneic conditions during sleep might have associations with altered HPA axis feedback mechanism and descending pain-inhibitory pathway impairment. Even though, the impacts of disrupted slow wave sleep structure on pain sensitization and jaw function could not be detected from the present study, the associations among deteriorated sleep structures owing to increased respiratory arousal, altered endocrinological homeostasis, and the development of hypersensitive myofascial TrPs in the masticatory muscles could be assumed.

One intriguing finding was that the significant differences of number of TrPs among the groups were only found in the masticatory muscles, not in the cervical muscles. Because this study was conducted in TMD and orofacial pain clinic, participants in this study might report less suffering from the cervical muscles than from the masticatory muscles.

To the best of our knowledge, the present study is the first attempt to reveal the potential associations among OSA, pain sensitization, and altered jaw function in the chronic pain-related TMD patients. However, there are some restrictions. To begin with, because the present study was a hospital-based study, the participants were recruited from a tertiary university hospital rather than from the community. Secondly, owing to the relatively small sample size, particularly among female OSA patients, the statistical power is inevitably compromised. In addition, this study may provide limited information about the role of sex in pain sensitization in OSA patients. Thirdly, the precise role of oxygen desaturation burden and hypoxemia on pain modulating mechanisms could not be derived due to lack of laboratory analysis. Future research with larger samples of participants including sufficient number of both male and female OSA patients recruited from the community should be required for further investigations.

In conclusion, complicated pain modulating mechanisms and jaw function could be influenced by diverse factors including oxygen desaturation, and sleep deprivation in patients with both pain-related TMD and OSA. Because there has been no consensus on the treatment protocol for pain-related TMD with OSA, it has not been established which disease should be treated first. TMD and orofacial pain specialists should consider not only symptoms of TMD but also OSA, because OSA could cause exaggerated orofacial pain perception and altered jaw function in patients with pain-related TMD. For better management of patients with both OSA and chronic TMD, thorough understanding of significant interactions between these two different conditions would be warranted. Interdisciplinary treatment including a physician, a dentist and an otolaryngologist is also warranted.

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Notes

Funding: This research was supported by a National Research Foundation of Korea grant funded by the Korean Government (2021R1H1A2093767).

Disclosure: All authors have no potential conflicts of interest to disclose.

Author Contributions:

Conceptualization: Kang JH, Kim HJ.
Methodology: Kang JH.
Formal analysis: Kang JH.
Fund acquisition: Kim HJ.
Data curation: Kang JH.
Validation: Kang JH.
Investigating: Kang JH.
Writing - original draft preparation: Kang JH.
Writing - review & editing: Kang JH, Kim HJ.

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References

1. Davies RJ, Stradling JR. The epidemiology of sleep apnoea. Thorax. 1996; 51(Suppl 2):S65–S70. PMID: 8869356.

2. Senaratna CV, Perret JL, Lodge CJ, Lowe AJ, Campbell BE, Matheson MC, et al. Prevalence of obstructive sleep apnea in the general population: a systematic review. Sleep Med Rev. 2017; 34:70–81. PMID: 27568340.

3. Yaggi HK, Strohl KP. Adult obstructive sleep apnea/hypopnea syndrome: definitions, risk factors, and pathogenesis. Clin Chest Med. 2010; 31(2):179–186. PMID: 20488280.

4. Rundo JV. Obstructive sleep apnea basics. Cleve Clin J Med. 2019; 86(9):Suppl 1. 2–9. PMID: 31509498.

5. Young T, Finn L, Peppard PE, Szklo-Coxe M, Austin D, Nieto FJ, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008; 31(8):1071–1078. PMID: 18714778.

6. Sánchez-de-la-Torre M, Campos-Rodriguez F, Barbé F. Obstructive sleep apnoea and cardiovascular disease. Lancet Respir Med. 2013; 1(1):61–72. PMID: 24321805.

7. Kang J, Tian Z, Wei J, Mu Z, Liang J, Li M. Association between obstructive sleep apnea and Alzheimer’s disease-related blood and cerebrospinal fluid biomarkers: a meta-analysis. J Clin Neurosci. 2022; 102:87–94. PMID: 35753156.

8. Park DH, Shin CJ, Hong SC, Yu J, Ryu SH, Kim EJ, et al. Correlation between the severity of obstructive sleep apnea and heart rate variability indices. J Korean Med Sci. 2008; 23(2):226–231. PMID: 18437004.

9. Yoon IY, Jeong DU. Degree of arousal is most correlated with blood pressure reactivity during sleep in obstructive sleep apnea. J Korean Med Sci. 2001; 16(6):707–711. PMID: 11748349.

10. 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 Breath. 2021; 25(4):2001–2006. PMID: 33674964.

11. 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. J Clin Sleep Med. 2014; 10(2):195–201. PMID: 24533003.

12. Roizenblatt S, Neto NS, Tufik S. Sleep disorders and fibromyalgia. Curr Pain Headache Rep. 2011; 15(5):347–357. PMID: 21594765.

13. Lee YH, Auh QS, An JS, Kim T. Poorer sleep quality in patients with chronic temporomandibular disorders compared to healthy controls. BMC Musculoskelet Disord. 2022; 23(1):246. PMID: 35287633.

14. Aytekin E, Demir SE, Komut EA, Okur SC, Burnaz O, Caglar NS, et al. Chronic widespread musculoskeletal pain in patients with obstructive sleep apnea syndrome and the relationship between sleep disorder and pain level, quality of life, and disability. J Phys Ther Sci. 2015; 27(9):2951–2954. PMID: 26504332.

15. Nadeem R, Bawaadam H, Asif A, Waheed I, Ghadai A, Khan A, et al. Effect of musculoskeletal pain on sleep architecture in patients with obstructive sleep apnea. Sleep Breath. 2014; 18(3):571–577. PMID: 24515853.

16. Kaczmarski P, Karuga FF, Szmyd B, Sochal M, Białasiewicz P, Strzelecki D, et al. The role of inflammation, hypoxia, and opioid receptor expression in pain modulation in patients suffering from obstructive sleep apnea. Int J Mol Sci. 2022; 23(16):23.

17. Doufas AG, Tian L, Padrez KA, Suwanprathes P, Cardell JA, Maecker HT, et al. Experimental pain and opioid analgesia in volunteers at high risk for obstructive sleep apnea. PLoS One. 2013; 8(1):e54807. PMID: 23382975.

18. 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(6):779–790. PMID: 19544755.

19. Maixner W, Greenspan JD, Dubner R, Bair E, Mulkey F, Miller V, et al. Potential autonomic risk factors for chronic TMD: descriptive data and empirically identified domains from the OPPERA case-control study. J Pain. 2011; 12(11):Suppl. T75–T91. PMID: 22074754.

20. Whale K, Gooberman-Hill R. The importance of sleep for people with chronic pain: current insights and evidence. JBMR Plus. 2022; 6(7):e10658. PMID: 35866153.

21. Choy EH. The role of sleep in pain and fibromyalgia. Nat Rev Rheumatol. 2015; 11(9):513–520. PMID: 25907704.

22. American Association of Orofacial Pain. Orofacial Pain Guidelines for Assessment, Diagnosis, and Management. Chicago, IL, USA: Quintessence;2013.

23. Park JW, Chung JW. Inflammatory cytokines and sleep disturbance in patients with temporomandibular disorders. J Oral Facial Pain Headache. 2016; 30(1):27–33. PMID: 26817030.

24. Almoznino G, Benoliel R, Sharav Y, Haviv Y. Sleep disorders and chronic craniofacial pain: characteristics and management possibilities. Sleep Med Rev. 2017; 33:39–50. PMID: 27321865.

25. Samsoon GL, Young JR. Difficult tracheal intubation: a retrospective study. Anaesthesia. 1987; 42(5):487–490. PMID: 3592174.

26. Brodsky L. Modern assessment of tonsils and adenoids. Pediatr Clin North Am. 1989; 36(6):1551–1569. PMID: 2685730.

27. Sateia MJ. International classification of sleep disorders-third edition: highlights and modifications. Chest. 2014; 146(5):1387–1394. PMID: 25367475.

28. Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012; 8(5):597–619. PMID: 23066376.

29. Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009; 5(3):263–276. PMID: 19960649.

30. Simon DG, Travell JG, Simon LS. Myofascial Pain and Dysfunction: the Trigger Point Manual. Baltimore, MD, USA: Williams & Wilkins;1999.

31. Charokopos A, Card ME, Gunderson C, Steffens C, Bastian LA. The association of obstructive sleep apnea and pain outcomes in adults: a systematic review. Pain Med. 2018; 19(Suppl 1):S69–S75. PMID: 30203008.

32. Doufas AG, Tian L, Davies MF, Warby SC. Nocturnal intermittent hypoxia is independently associated with pain in subjects suffering from sleep-disordered breathing. Anesthesiology. 2013; 119(5):1149–1162. PMID: 24025612.

33. Dreweck FD, Soares S, Duarte J, Conti PC, De Luca Canto G, Luís Porporatti A. Association between painful temporomandibular disorders and sleep quality: A systematic review. J Oral Rehabil. 2020; 47(8):1041–1051. PMID: 32395855.

34. Olmos SR. Comorbidities of chronic facial pain and obstructive sleep apnea. Curr Opin Pulm Med. 2016; 22(6):570–575. PMID: 27662470.

35. Sanders AE, Essick GK, Fillingim R, Knott C, Ohrbach R, Greenspan JD, et al. Sleep apnea symptoms and risk of temporomandibular disorder: OPPERA cohort. J Dent Res. 2013; 92(7):Suppl. 70S–77S. PMID: 23690360.

36. Yokoe T, Minoguchi K, Matsuo H, Oda N, Minoguchi H, Yoshino G, et al. Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure. Circulation. 2003; 107(8):1129–1134. PMID: 12615790.

37. Fang D, Kong LY, Cai J, Li S, Liu XD, Han JS, et al. Interleukin-6-mediated functional upregulation of TRPV1 receptors in dorsal root ganglion neurons through the activation of JAK/PI3K signaling pathway: roles in the development of bone cancer pain in a rat model. Pain. 2015; 156(6):1124–1144. PMID: 25775359.

38. Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci. 2008; 28(20):5189–5194. PMID: 18480275.

39. Ji RR, Nackley A, Huh Y, Terrando N, Maixner W. Neuroinflammation and central sensitization in chronic and widespread pain. Anesthesiology. 2018; 129(2):343–366. PMID: 29462012.

40. de Feijter M, Katimertzoglou A, Tiemensma J, Ikram MA, Luik AI. Polysomnography-estimated sleep and the negative feedback loop of the hypothalamic-pituitary-adrenal (HPA) axis. Psychoneuroendocrinology. 2022; 141:105749. PMID: 35427952.

41. Jo KB, Lee YJ, Lee IG, Lee SC, Park JY, Ahn RS. Association of pain intensity, pain-related disability, and depression with hypothalamus-pituitary-adrenal axis function in female patients with chronic temporomandibular disorders. Psychoneuroendocrinology. 2016; 69:106–115. PMID: 27082645.

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