Effects of CO Level on Pain, Sensory Function, and Subjective Health

Evaluation of the Effects of Carbon Monoxide (CO) Levels on Pain Threshold, Sensory Function, Anxiety, Depression, and Subjective Health Complaints

Carbon monoxide (CO) is a colorless and odorless gas that can enter the human body through environmental exposure and especially tobacco use. CO binds to hemoglobin with a much higher affinity than oxygen, thereby reducing oxygen transport to tissues. This condition may lead to various physiological and psychological effects, particularly on the nervous system.

In the literature, CO exposure has mainly been investigated in the context of acute poisoning cases and smoking-related effects. However, studies evaluating the effects of low-level and chronic CO exposure-more commonly encountered in the general population-on pain perception, sensory functions, and psychological status are limited.

Tobacco smoke is an important source of CO, and exhaled CO levels have been shown to be significantly higher in smokers and associated with various neurocognitive changes. Evidence suggests that CO exposure may influence anxiety, depression, attention, and cognitive functions. In addition, some studies indicate that CO may affect brain regions involved in pain perception and emotional regulation.

However, there is insufficient research examining the relationship between low-level carbon monoxide exposure and pain threshold, sensory functions, anxiety, depression, and subjective health complaints within the same study framework.

This study aims to evaluate the relationship between exhaled carbon monoxide (CO) levels and pain threshold, sensory functions, anxiety, depression, and subjective health complaints in healthy adults. By examining the multidimensional effects of low-level CO exposure, the study seeks to fill an important gap in the literature and provide a more comprehensive understanding of this issue.

Study Overview

• Status: Not yet recruiting
• Conditions: Carbon Monoxide, Pain Perception, Sensory Thresholds, Anxiety, Depression, Tobacco Smoking

Detailed Description

Carbon monoxide (CO) is a colorless, odorless, and toxic gas that can adversely affect human health through both environmental and behavioral exposure pathways. In the literature, most studies on CO exposure have focused on acute poisoning cases and smoking cessation processes. In contrast, research addressing the physiological and psychological effects of chronic low-level CO exposure, which is more commonly encountered in the general population, remains limited.

According to the World Health Organization (WHO), tobacco use causes approximately 8 million deaths annually and represents a major public health concern. CO, one of the main components of tobacco smoke, binds to hemoglobin with a much higher affinity than oxygen, impairing oxygen transport to tissues and leading to systemic hypoxia. This condition has particularly pronounced effects on the central nervous system.

Studies on the neurological and psychiatric outcomes of CO exposure have reported that cognitive impairments, anxiety, and depressive symptoms are frequently observed following acute poisoning. Significant associations have also been demonstrated between the severity of poisoning and the level of depressive and anxious symptoms. In addition, voxel-based morphometry studies have reported that CO exposure may lead to reductions in gray matter volume in brain regions associated with pain perception and emotional regulation, such as the frontal lobe, cerebellum, and periaqueductal gray matter.

In studies involving smokers, exhaled CO levels have been shown to be significantly higher compared to non-smokers and positively correlated with daily cigarette consumption. Even at low carboxyhemoglobin levels, neurological effects such as visual perception impairments, attention deficits, learning difficulties, and reduced motor performance have been reported.

At the molecular level, CO is thought to induce oxidative stress and neuroinflammatory processes, potentially leading to neuronal damage. These mechanisms may influence pain perception, sensory functions, and emotional status. However, studies simultaneously evaluating the relationship between chronic low-level CO exposure and pain threshold, sensory function, anxiety, depression, and subjective health complaints are still insufficient.

In this context, the planned study aims to systematically and comprehensively evaluate the relationships between exhaled carbon monoxide (CO) levels and pain threshold, sensory functions, anxiety, depression, and subjective health complaints in healthy adults. The study is expected to fill an important gap in the literature by shedding light on the multidimensional effects of chronic low-level CO exposure and contributing novel insights to the scientific knowledge base.

• Study Type: Observational
• Enrollment (Estimated): 70

Contacts and Locations

• Study Contact: Name: Betül Taşpınar, Professor; Phone Number: +90 506 680 44 26

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will include healthy adult participants aged 18-65 years with a history of regular smoking for at least the past 6 months. Participants will be free of respiratory, cardiovascular, neurological, and psychiatric diseases, and will not have any acute infection or recent surgery affecting respiratory muscles.

Description

Inclusion Criteria:

• Being between the ages of 18 and 65

Having a regular smoking history for the past 6 months

No history of respiratory, cardiovascular, or neurological/psychiatric diseases

No recent surgery or trauma that could affect respiratory muscles

Not having an acute infection (especially upper or lower respiratory tract infection)

Exclusion Criteria:

-

Having chronic respiratory diseases such as COPD or asthma

Having a history of cardiovascular disease

Having a diagnosed neurological or psychiatric disorder

Having a history of surgery or trauma affecting respiratory muscles within the last 3 months

Being pregnant or having a suspicion of pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Healthy Adults - CO Exposure; This cohort includes healthy adult participants. No intervention is applied. Participants will be assessed for exhaled carbon monoxide (CO) levels, pain threshold, sensory functions, anxiety, depression, and subjective health complaints. The study aims to investigate the association between low-level CO exposure and physiological and psychological outcomes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exhaled Carbon Monoxide (CO) Level	Exhaled carbon monoxide levels will be measured using a Bedfont Smokerlyzer-piCO+ device. Participants will be instructed to take a deep breath, hold their breath for 15 seconds, and then exhale slowly and completely into the device mouthpiece. The measured CO values will be classified as follows: 0-6 ppm: non-smoker 7-10 ppm: light exposure 11-15 ppm: regular smoker 16-25 ppm: heavy smoker 25 ppm: very heavy smoker	June 2026- July 2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Threshold Measurement	Pressure pain thresholds will be assessed using an algometer, which is a validated and reliable tool for measuring muscle and soft tissue sensitivity. The device consists of a 1 cm diameter rubber-tipped metal probe attached to a pressure gauge measuring force in kilograms and pounds. Pressure pain thresholds will be measured bilaterally at the upper, middle, and lower portions of the trapezius muscle	June 2026- July 2026
Beck Anxiety Inventory (BAI)	Anxiety levels will be assessed using the Beck Anxiety Inventory, a 21-item self-report questionnaire. Each item will be scored between 0 and 3, with total scores ranging from 0 to 63. Higher scores will indicate greater anxiety severity.	June 2026- July 2026
Beck Depression Inventory (BDI)	Depressive symptoms will be evaluated using the Beck Depression Inventory, a 21-item self-report scale assessing cognitive, emotional, motivational, and somatic symptoms of depression. Each item will be scored from 0 to 3, with total scores ranging from 0 to 63. Higher scores will indicate more severe depressive symptoms.	June 2026- July 2026
Semmes-Weinstein Monofilament Test	Sensory function will be assessed using the Semmes-Weinstein monofilament test, a widely used method for evaluating light touch and pressure perception. Monofilaments ranging from 0.086 gm to 448 gm will be applied in ascending order. Testing will be performed from distal to proximal regions, including the anterior and posterior surfaces of all fingers. The smallest detectable monofilament will be recorded. When the filament bends, the applied force will be considered constant, and participants' perception will be recorded accordingly	June 2026- July 2026
Subjective Health Complaints Inventory	Physical and psychological health complaints will be assessed using the Subjective Health Complaints Inventory, a self-report questionnaire developed in Norway and widely used internationally. The scale consists of 29 items rated from 0 (none) to 3 (severe), covering symptoms experienced during the last 30 days. Total scores will range from 0 to 87, with higher scores indicating more complaints. The scale includes five subdomains: musculoskeletal, pseudoneurological, gastrointestinal, allergy, and flu-like symptoms.	June 2026-July 2026
Fagerström Test for Nicotine Dependence	Nicotine dependence will be assessed using the Fagerström Test for Nicotine Dependence, a 6-item self-report questionnaire. Total scores will range from 0 to 10. Based on the score, participants will be classified as very low, low, moderate, high, or very high dependence.	June 2026- July 2026

Collaborators and Investigators

• Sponsor: Izmir Democracy University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: pain threshold; healthy adults; sensory function; CO exposure; exhaled carbon monoxide; smoking and CO
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Behavior; Tobacco Use; Anxiety Disorders; Depression; Smoking; Tobacco Smoking
• Other Study ID Numbers: 2026/3-6

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared due to privacy and confidentiality considerations. All data will be analyzed and reported in an aggregated and anonymized form to ensure participant protection.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No