Sleep and Pain Sensitivity

Sponsor

Aalborg University (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04246294

Collaborator

Aalborg University Hospital (Other)

124

Enrollment

Location

Anticipated Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This project will assess patients with diagnosed obstructive sleep apnea, to investigate the impact of poor sleep on central pain mechanisms. Furthermore, the project will explore if restoring good sleep hygiene can improve the central pain mechanisms that may be associated with the risk of chronic pain.

Condition or Disease	Intervention/Treatment	Phase
Sleep Apnea Chronic Pain Syndrome	Device: Continuous Positive Airway Pressure (CPAP)

Detailed Description

Chronic pain affects approx. 20% of the world's population and greatly affects the quality of life of the patients. Recent studies have found that multiple chronic pain patients are characterized by central sensitization and other studies have even found that the degree of central sensitization might be important for pain relieving effects to, e.g., surgery or pharmaceutical treatment. These studies highlight the importance of assessing central sensitization but also indicate that central sensitization can be influenced by multiple factors and it is deemed important to assess such factors in experimental and clinical settings to improve our understanding of the field.

Sleep impairment and the effects on central pain pathways One common complaint among chronic pain patients is that their sleep is affected. It is estimated that at least 50% of chronic pain patients also suffer from sleep disturbances. This is alarming since sleep is well-known to provide neural maturation, facilitate learning, memory, cognition, and general productivity and a lack of sleep impact all of these important processes. Furthermore, earlier studies have shown that partial and total sleep deprivation affect even healthy participants and impair both peripheral and central pain pathways and may indicate that regular sleep is important to maintain a proper healthy response to pain. This notion is supported by evidence showing an association between sleep impairment (e.g. partial or total sleep deprivation) and impaired conditioned pain modulation (CPM), which is the human surrogate model for diffuse noxious inhibitory control. It is also well-established that CPM is impaired in chronic pain patients suffering from back pain, fibromyalgia, or severe knee osteoarthritis (OA). Davies et al. demonstrated that restoring sleep could predict resolution of chronic widespread pain. However, the underlying mechanisms linking impaired sleep and a reduction in pain inhibition are still unclear. Certain neurotransmitters such as serotonin and brain areas such as the periaqueductal gray matter are known to modulate both sleep stages and nociception, and may partly explain the association between impaired sleep and reduction in pain inhibition.

Nonetheless, little is known about the effect of sleep impairment on central pain mechanisms in clinical cohorts. This is important since it is still unclear if restoring a good quality of sleep can modulate the central pain pathway changes known to occur when having impaired sleep and/or chronic pain.

One approach to this question is to assess patients known to suffer from sleep impairment. In this respect, obstructive sleep apnea (OSA) patients are known to present with worsened sleep due to the collapse of the pharyngeal musculature throughout the night. This leads to excessive daytime sleepiness and a decrease in quality of life. Furthermore, pain tolerance has been shown to be decreased in elderly who are diagnosed with OSA. However, little is known about OSA patients and pain sensitivity, and if the sleep impairment also affects the central pain pathways. If so, this may provide an important first step in understanding the possible benefit of restoring restoring normal regular sleep, as routinely achieved through gold standard treatment, and if this can modulate central changes known to occur in chronic pain patients.

Therefore, this project will focus on obstructive sleep apnea (OSA) patients to investigate if central pain mechanisms are affected by poor sleep and if golden standard sleep therapy through continuous positive airway pressure (CPAP) improves central pain mechanisms.

Study Design

Study Type:

Observational

Anticipated Enrollment :

124 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Sleep and Pain Sensitivity

Actual Study Start Date :

Feb 1, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Sleep apnea patients This group of patients will have been monitored over night with cardiorespiratory monitoring (CRM). CRM enables the physician to establish an Apnea-Hypopnea Index (AHI) which will be used for diagnosis. An AHI > 15 is considered moderate-to-severe sleep apnea, and this is the focus group of patients in the current project. These patients will be followed for 12 months during continuous positive airway pressure (CPAP) treatment. Adherence to the CPAP treatment will be closely monitored.	Device: Continuous Positive Airway Pressure (CPAP) CPAP is golden standard treatment for moderate-to-severe sleep apnea with high compliance, effectiveness, and cost-effectiveness. There will be no interference with standard care.

Arm

Intervention/Treatment

Sleep apnea patients

This group of patients will have been monitored over night with cardiorespiratory monitoring (CRM). CRM enables the physician to establish an Apnea-Hypopnea Index (AHI) which will be used for diagnosis. An AHI > 15 is considered moderate-to-severe sleep apnea, and this is the focus group of patients in the current project. These patients will be followed for 12 months during continuous positive airway pressure (CPAP) treatment. Adherence to the CPAP treatment will be closely monitored.

Device: Continuous Positive Airway Pressure (CPAP)

CPAP is golden standard treatment for moderate-to-severe sleep apnea with high compliance, effectiveness, and cost-effectiveness. There will be no interference with standard care.

Outcome Measures

Primary Outcome Measures

Change in daytime sleepiness due to sleep apnea [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Daytime sleepiness as assessed by Epworth Sleepiness Scale, will be evaluated as a change from before treatment initiation (min value: 0 (no daily sleepiness); max value (24) - higher score associated with increased sleepiness)

Secondary Outcome Measures

Change in pain inihibition and facilitation [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Cuff-algometry will be used to assess pain inhibition and facilitation, which are human surrogate models for central pain mechanisms. For this, mechanical pressure will be applied to the lower dominant and non-dominant leg. Pain inhibition will be calculated as the difference in mechanical pressure threshold and tolerance on the dominant leg, with and without a conditioning pressure applied to the non-dominant leg. Furthermore, pain facilitation will be assessed by applying 10 rapid mechanical stimuli in succession to the dominant lower leg, at the same pressure intensity.
PainDetect [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Questionnaire for occurrence of neuropathic-like symptoms. The scale ranges from 0-38 based on 9 items. A score > 19 indicates that there are neuropathic-like symptoms, whereas scores < 12 suggest nociceptive symptoms. Scores between 13 and 18 are indicative of unclear symptoms.
Pain Catastrophizing Scale [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Questionnaire for assessing level of pain catastrophizing thoughts. The scale ranges from 0-52, where scores > 30 indicates clinical pain catastrophizing. The scale consists of 13 items which are scored from 0-4. This scale is validated in both chronic pain patients, and pain-free individuals.
Pain intensity [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Evaluation of the presence of pain. The scale is based on a 0-10 score, where 0 represents no pain, and 10 represents worst pain imaginable. The patients will be asked to indicate whether they have pain at the time of inclusion, at 1 month, and 12 months after treatment initiation.
Continuous Positive Airway Pressure compliance (percentage who continues using the device for the optimum amount of time each night) and adherence (the percentage of patients who abandon treatment completely) [Baseline - 1 month- 12 months after initiation of sleep apnea treatment]
Usage of the CPAP treatment. Compliance will be based on the percentage of patients that continue using the treatment device for more than 4 hrs each night. This will be assessed throughout the study period to ensure sufficient sample size and subgrouping of compliant and non-compliant patients. Patients will be asked whether or not they still use the device and if so, how many hours a night. Adherence will be assessed by the total amount of patients who abandon treatment throughout the project period.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women presenting with an apnea-hypopnea (AHI) index > 15 (moderate-to-severe sleep apnea) measured by cardiorespiratory monitoring (CRM) and scheduled for treatment at Søvncenter Nord
Age 18-80

Exclusion Criteria:

Pregnancy
Intake of drugs labelled with the red warning triangle and misuse of cannabis and opioids
No previous or current neurologic or mental illnesses
Lack of ability to cooperate
Non-fluent in Danish (reading, speaking, and comprehension)