Natl. J. Physiol. Pharm. Pharmacol. (2025), Vol. 15(1): 49-53

Research Article

10.5455/NJPPP.2025.v15.i1.8

Assessment of cardiovascular reflex tests in fibromyalgia patients

Ezmat Jalil¹, Enam Ahmad¹, Waqas Alauddin² and Prajakta Radke^3*

¹Department of Physiology, Government Medical College and Super Facility Hospital, Azamgarh, India

²Department of Physiology, Naraina Medical College and Research Centre, Kanpur, India

³Department of Physiology, MGM Medical College, Navi Mumbai, India

*Corresponding Author: Prajakta Radke. Department of Physiology, MGM Medical College, Navi Mumbai, India. Email: prajaktaradke [at] gmail.com

Submitted: 22/08/2024 Accepted: 13/12/2024 Published: 31/01/2025

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Abstract

Background: Fibromyalgia is caused by various elements, such as hereditary, physical, and psychological, along with social influences. Alterations to the neurological system, including in the brain’s circuitry and cognitive-emotional regions, are associated with chronic pain. According to the neurovisceral integration paradigm, there is a complicated interaction between visceral structures and autonomic dysfunction.

Aim: This study aims to assess autonomic reactivity in both healthy controls and fibromyalgia patients.

Methods: Out of 60 individuals, 30 were classified as having fibromyalgia by the medicine department, while 30 were healthy controls. Each subject underwent and recorded cardiovascular reflex tests, such as the Valsalva maneuver, deep breathing test (DBT) examinations, handgrip examinations, cold pressor tests, and lying-to-stand tests (LSTs). SPSS edition 21 was used for the statistical analysis. The unpaired t-test was applied to parameters with normal distributions.

Results: Patients with fibromyalgia showed a significant decrease in their delta heart rate during DBT (13.11 ± 1.19 vs. 15.26 ± 1.34, p < 0.001) compared to the controlled group. The expiration:inspiration (E:I) ratio during DBT in fibromyalgia patients was significantly decreased (1.19 ± 0.21 vs. 1.30 ± 0.49, p < 0.001) compared to the controlled group, and the Valsalva ratio in fibromyalgia patients was also substantially reduced (1.17 ± 0.65 vs. 1.48 ± 0.78, p < 0.001) compared to the controlled group. The fibromyalgia patients exhibited a significant fall in systolic blood pressure during LST (11.93 ± 4.84 vs. 3.89 ± 2.12, p < 0.001) compared to the control group. The 30:15 ratio during LST in fibromyalgia patients was significantly reduced (1.13 ± 0.22 vs. 1.24 ± 0.37, p < 0.001) in comparison to the healthy control group. The rise in heart rate during LST was substantially greater in patients with fibromyalgia (13.32 ± 5.28 vs. 8.34 ± 3.71, p < 0.001) compared to the control group. The cold pressor test was significantly decreased in fibromyalgia patients (9.29 ± 4.01 vs. 15.92 ± 5.64, p < 0.001) when compared to the control group. The handgrip test findings were statistically insignificant.

Conclusion: Revealing autonomic dysfunction, the parasympathetic tone was lower as well as sympathetic impairment was observed in fibromyalgia patients compared to the healthy control group. Future studies should concentrate on autonomic nervous system dysfunction as a biomarker for early warning signals for drug intake and fibromyalgia treatment.

Keywords: Autonomic dysfunction, Fibromyalgia, Cardiovascular autonomic reactivity, Sympathetic tone, Parasympathetic tone.

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Introduction

A complex condition, fibromyalgia syndrome (FMS) is characterized by body pain, stiffness and soreness, fatigue, mood swings and irregular sleep, depression, and cognitive decline (Arnold et al., 2011). Numerous elements, such as genetic, physical, mental, and societal ones, are frequently linked to low back pain (Hartvigsen et al., 2018). The information that is currently available indicates that conditions that are characterized by pain that persists are linked to modifications in the architecture and operation of the whole nervous system, which includes the brain, the spinal column, as well as peripheral receptors (Apkarian, 2013; Wager et al., 2013).

In this paradigm, changes in sensory perception and motor function, as well as an intricate brain system that incorporates inputs from within as well as outside the body, are responsible for integrating physiological cognitive and behavioral responses, perception, and action (Thayer et al., 2010). This theory states that the amygdala, which is regulated by threat and uncertainty, may have an effect on the signals sent to the autonomic nervous system (ANS) by the prefrontal cortex (Shekhar et al., 2003). One method to assess the relationship between the heart and CNS is to measure the heart rate variability (HRV), a noninvasive technique that is used to characterize fluctuations between successive RR intervals on an electrocardiogram (ECG) and evaluate the cardiac sinus node’s ANS modulation (Malik, 1996).

Previous studies have found that patients with FMS reported higher pain intensity ratings and a lower pain threshold and tolerance, as exaggerated pain sensitivity may be caused by diminished sympathetic and parasympathetic impacts when the cold pressor test was performed, revealing impaired autonomic cardiovascular regulation and decreased sympathetic reactivity to acute stress (Reyes del Paso et al., 2011). Fibromyalgia patients also had lower reactivity to postural changes compared to healthy women, and autonomic adjustments to postural changes were inversely associated with the severity of clinical pain, thus suggesting autonomic dysfunction in the early stages of fibromyalgia (Contreras-Merino et al., 2022).

One study found that FM patients showed higher total peripheral resistance but lower stroke volume and cardiac output on the effect of gravitational stress lying-to-standing test (LST) due to orthostatic challenges and redistribution of blood volume, indicating sympathetic dysfunction (Reyes Del Paso et al., 2024).

There is a paucity of studies in fibromyalgia patients where cardiovascular reflex tests are performed, as previous studies have been done using HRV. Thus, the aim of this study was to delve into autonomic dysfunctions in fibromyalgia patients, thus evaluating their sympathetic and parasympathetic impairment by cardiovascular reflex tests, including the Valsalva maneuver, LST, deep breathing tests (DBTs), handgrip tests, and cold pressor tests.

The significance of this investigation was brought about by earlier studies that used HRV to determine autonomic dysfunction. As far as we are aware, this is the first study among the Indian population where patients with fibromyalgia will undergo cardiovascular reflex testing.

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Materials and Methods

This cross-sectional research was conducted at the Department of Physiology in collaboration with the Department of Medicine comprising a total of 60 subjects, 30 in the fibromyalgia group and 30 in the healthy control group, aged 25–40 years old and representing both sexes. Thirty diagnosed patients with chronic fibromyalgia based on the American College Rheumatology 2016 criteria were chosen within the outpatient clinic of medicine. After providing informed written consent, cardiovascular reflex tests were performed. Substance abuse disorders, dysfunction of the autonomic system, hepatorenal or endocrine diseases, arterial hypertension, heart disease, type 2 diabetes, neurological or mental illnesses, and other serious medical conditions were not allowed in order to maintain a homogeneous study population.

In accordance with accepted procedures documented in the literature, a battery of tests, such as deep breathing, Valsalva maneuver, lying to standing, cold pressor, and hand grip test, were conducted (Alauddin et al., 2024). The experimental protocol required the subjects to abstain from food and caffeine for 4 hours before the tests were conducted. During each test, the Lead II ECG on ECG machine and brachial artery blood pressure were recorded using a digital sphygmomanometer. Participants were instructed not to eat or drink caffeine for 4 hours before the experiment in order to reduce the possibility of confusion.

DBT is a method used to measure cardiac parasympathetic activity, as the vagus nerve, responsible for regulating heart rate (HR), is stimulated by deep breathing. The technique involves six slow, deep breathing phases lasting 10 seconds, with the HR and RR intervals calculated using ECG data. The delta HR is the difference, averaged over six cycles, that exists between maximal and minimal HRs during inspiration and expiration is known as delta HR. The proportion of the longest to the shortest R-R interval, averaged over six cycles, is known as the E:I ratio.

The LST evaluates both ANS limbs; changes in systolic blood pressure (SBP) show how responsive the sympathetic system is, while the 30:15 ratio shows how responsive the parasympathetic limb is. After receiving thorough instructions, the test is administered following 10 minutes of supine rest. Recordings are made after the subject is instructed to achieve the standing position in three seconds. The 30:15 ratio is the ratio of the longest R-R interval that occurs around the 30th beat to the shortest R-R interval at or around the 15th beat. The change in SBP is the baseline SBP minus the maximum fall in SBP on standing.

The Valsalva method is another technique used to measure cardiovagal activity or parasympathetic nervous system activity. Participants are instructed to forcefully breathe into a mouthpiece attached to a sphygmomanometer for 15 seconds to maintain an exhalation pressure of 40 mmHg. The Valsalva ratio (VR) is determined by dividing the greatest RR intervals (phase 4) by the shortest gap (phase 2).

A supervised isometric handgrip exercise is used to measure diastolic blood pressure (DBP) variations to assess sympathetic nervous system activity, particularly adrenergic function.

The cold pressor examination measures DBP, or reactivity to cold stimuli, to evaluate sympathetic adrenergic activity. The subject is instructed to immerse their hand in cold water for a minute, and their arterial pressure is measured to determine if it rises above the baseline.

The statistical evaluation

IBM SPSS Statistics for Windows, Version 21.0, was the statistical program used in this study for data management, analysis, and interpretation. After gathering data for the control and chronic fibromyalgia groups using descriptive statistics such as means and standard deviations (SD), the researchers gave their findings. To determine whether there had been any statistically significant variations between the groups, the researchers employed an unpaired t-test. A two-tailed p-value of less than 0.05 was established as the threshold for statistical significance.

The Institutional Ethics Review Committee of the Government Medical College & Superfacility Hospital in Azamgarh, Uttar Pradesh, granted permission to carry out this investigation.

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Results

There were 60 participants in this study, including both healthy controls and fibromyalgia patients. The mean age of fibromyalgia patients was 38.23 ± 3.84 years with 19 males and 11 females. The average age of the healthy population was 36.12 ± 4.56 years with 18 males and 12 females. The mean age was statistically insignificant (p=0.732). According to Table 1, the average HR of fibromyalgia patients was 83.49 ± 3.69, while the average HR of healthy individuals was 82.67 ± 5.01 beats per minute (bpm).

Table 1. Basal parameter comparison between healthy controls and those with fibromyalgia.

Table 2. Cardiovascular reflex test compared to healthy controls and patients with fibromyalgia.

According to Table 2, the delta HR (DBT) of fibromyalgia patients was 13.11 ± 1.19, while the DBT was 15.26 ± 1.34 (p < 0.001*). The E:I ratio (DBT) was 1.19 ± 0.21 for fibromyalgia patients and 1.30 ± 0.49 for healthy people (p < 0.001*). Table 2 shows that the values of the VR were 1.17 ± 0.65 for patients with fibromyalgia and 1.48 ± 0.78 for healthy people (p < 0.001*). The 30:15 ratio as well as SBP (LST) of the fibromyalgia patients significantly decreased when compared to the healthy group of controls (p < 0.001*). HR (LST) increased significantly in fibromyalgia patients, rising 13.32 ± 5.28 versus 8.34 ± 3.71 in the control (p < 0.001*). The cold pressor test results were significantly different (p < 0.001*) when comparing the fibromyalgia patients to the control group. Table 2 displays the statistically insignificant (p=0.090) results of the handgrip test.

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Discussion

We discovered that parasympathetic responsiveness tests were decreased and significant sympathetic impairment was observed in fibromyalgia patients. In patients with fibromyalgia, the E:I ratio decreased statistically significantly (1.19 ± 0.21). The optimum proportion is 1.21:1.10 is considered abnormal, whereas 1.11:1.20 is considered borderline. Compared to the control group, the fibromyalgia patients had a lower E:I ratio with ∆HR values. As we discovered, numerous studies demonstrate autonomic dysfunctions.

Lower mean values across all HRV frequency domains were discovered by Reyes del Paso et al. (2010) suggesting a general decline in HRV and autonomic disorders in fibromyalgia patients. Hallman and Lyskov (2012) investigated everyday stress perception, activity levels, and ANS control in a study of 55 people who had chronic neck and shoulder pain. The authors found shorter RR intervals and lower HRV when comparing their results to those of the control group. According to these findings, the parasympathetic tone activation was lower in the group experiencing chronic pain (Hallman and Lyskov, 2012). Additionally, we found that patients with fibromyalgia had a substantially lower E:I ratio with ∆HR values, which indicates parasympathetic reactivity and a reduction in parasympathetic tone with sympathetic dysfunction. Tracy and colleagues’ study looked at how HRV changed in people with chronic pain conditions such as fibromyalgia, mandibular disorders, persistent shoulder and pain in the neck, and persistent pain in the back (Tracy et al., 2016). They discovered a link between a decline in HRV and chronic pain conditions, especially in data pertaining to the high frequency (HF) subdomain. VR was significantly lower in the fibromyalgia unit (mean=1.17 ± 0.65; p < 0.001*) than in the control group (mean=1.48 ± 0.78). In general, there ought to be a VR variation of ≥1.21, even though the readings for both groups were within the anticipated range. A value of 1.10 is considered abnormal, whereas readings of 1.11 and 1.20 constitute the borderline. The fibromyalgia group had a lower LST 30:15 ratio (mean=1.13 ± 0.22) than the control group (mean=1.24 ± 0.37). The difference was statistically significant at p < 0.001. After examining 62 patients with persistent low back pain, Telles et al. (2016) found that the LF-HRV measure (sympathetic dysfunction) predominated in their subjects. Zhang et al. (2008) discovered that low frequency outnumbered HF; however, these investigations did not include a control group that consisted of people in good health. The same conclusion was reached by our research. Test results for parasympathetic reactivity and sympathetic tone were significantly lower in fibromyalgia patients, suggesting autonomic dysfunction. According to Gockel et al. (2008), people with intermediate disability compared to those who had no disability had lower HRV, higher pain intensity, and high levels of disability. Koenig et al. (2016) discovered that people with chronic neck pain had lower HF, indicating decreased parasympathetic tone and higher levels of catastrophizing when compared to healthy controls. Our findings also showed the same thing.

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Study strengths

Cardiovascular reflex test measurement at rest may be a crucial clinical tool for fibromyalgia patients. Additionally, compared to the healthy control group, our data showed a significant sympathetic impairment and a decrease in parasympathetic reactivity. This implies that patients with fibromyalgia exhibit a decrease in parasympathetic reactivity and sympathetic dysfunction. The gold standard test for assessing autonomic functions is the cardiovascular reflex test. The results of these tests may provide important information about the long-term likelihood of predicting the morbidity and mortality of cardiovascular problems in fibromyalgia patients.

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Study limitations

One of the study’s limitations was the small sample size of only 30 patients. For more detailed results, a larger sample size is required.

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Conclusion

Our results point to a possible connection between autonomic impairment and fibromyalgia. In patients with fibromyalgia, the study found signs of sympathetic impairment and decreased parasympathetic tone. The results of these tests may provide important information about the long-term likelihood of predicting the mortality and morbidity outcomes of cardiovascular problems in fibromyalgia patients. Additionally, these tests may serve as a minimally invasive screening method to determine the presence and severity of autonomic dysfunction in fibromyalgia patients.

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