Discussion
We have shown that autonomic nervous system function assessed with the HRV method differs between sciatica patients referred to spine surgery and healthy controls. Vagally mediated HF power and SD1 were significantly lower in the patients than in the healthy controls, whereas the short-term fractal scaling exponent α1, indicating sympathovagal balance, was higher in the patients than in the controls after adjusting for potential confounders. Impaired functional capacity caused by pain or pain intensity was not associated with HRV among the patients, but HF power correlated negatively with LBP duration. Since altered HRV has been shown to have a prognostic value in both healthy subjects and various patient groups, the present results may provide important clues for understanding and considering the contribution of autonomic nervous system function in sciatica patients referred to spine surgery.
Heart Rate Variability Among Low Back Patients
It is well documented that gender, BMI, smoking, and physical activity affects HRV. Although there were more smokers, higher BMI, less high LTPA, and more men in the patient group than in the controls, HRV still differed between the groups when these potential confounders were accounted for. Additionally, the association remained evident after accounting for underlying co-morbidities and in separate sub-analysis where the patients with and without HNP-induced sciatica were compared. Taken together, obvious differences between the patient and control groups were observed in pain intensity (VAS score) and perceived disability (Oswestry), emphasizing the independent role of pain in HRV.
In a previous study, higher HF power was observed among patients with chronic LBP whose Oswestry score was less than 20% compared with patients whose score was 20–40%, but HF power did not differ between patients whose VAS score was 0–5 vs. 6–10. In the present study, we could not find an association between HF power and Oswestry or VAS score, whereas HF power correlated with pain duration, i.e. decreased vagal outflow was related to prolonged pain. Since in our study attenuated vagal activity during orthostatic stress was not linked to pain intensity or impaired functional capacity, it might be aggravated by the chronicity of the disease measured by the duration of pain. This finding may suggest that the dysfunction of the autonomic nervous system is a feature of the current pain condition and not related to pain severity per se.
Potential Mechanisms for Decreased Heart Rate Variability Among the Patients
It has been evidenced for a long time that various states of chronic pain, including LBP, are associated with signs of altered autonomic nervous system function, but the physiological mechanisms remain unclear. A recent study showed that HRV was reduced in complex regional pain syndrome (CRPS) patients compared with controls. During orthostatic stress, patients with CRPS were not able to preserve cardiac output and they had an exaggerated increase in total peripheral resistance. Interestingly, the hemodynamic changes correlated with pain duration but not with pain intensity, e.g. a tilt-induced increase in total peripheral resistance correlated positively with pain duration. Furthermore, in patients with chronic widespread pain (CWP), lower HRV is associated with higher pain intensity. Interestingly, a recent study by Kang et al. showed that different disease profiles can be determined by clustering distinct features in patients with chronic neck pain. According to this study, a high degree of disability associated with low HRV, high pain intensity, older age, poor sleep quality and high psychological distress. These findings may suggest a general autonomic imbalance in both CRPS, CWP and chronic neck pain patients, which may also be the status of our sciatica patients referred to spine surgery.
Recent studies have shown that the production of proinflammatory markers within the nucleus pulposus may be an important mediator in discogenic pain. Elevated levels of serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with a herniated lumbar intervertebral disc or elevated IL-6 in patients with lumbar radiculopathy, compared with healthy subjects, have been observed. Interestingly, autonomic dysregulation, expressed as depressed HRV, has been linked to increased IL-6 in healthy individuals as well as in those with a cardiovascular disease. Therefore, it could be hypothesized that autonomic dysfunction observed in the sciatica patients in the present study may be related to increased cytokine production by the immune system. However, this should be confirmed in future studies.
Methodological Considerations
In the present study, we assessed HRV in a supine position and also during orthostatic stress in a standing position. It is well documented that HRV is susceptible to saturation when measured at a low HR, which is usually the case in a supine position, and it may therefore be unable to detect changes in cardiac vagal outflow. Additionally, vagal and sympathetic regulation operates in a reciprocal fashion during a sympathetic orthostatic stimulus. Therefore, a standing position might be a more favorable condition than supine for measuring autonomic function, since it could detect attenuated vagal outflow related to increased sympathetic activity, as well. Indeed, in the present study we found a clearer difference in HRV indices measured in a standing position then in a supine position.
It is also noteworthy that we measured the fractal scaling exponent α1 as an index of sympathovagal balance, because this index has been shown to provide information on autonomic interactions during various interventions and is less sensitive than spectral measures to trends and non-stationarities in HR behavior. In the present study, the LF/HF ratio was higher in the patients than in the controls in a standing position, but after adjusting for sex, smoking, BMI, and LTPA, the difference between the groups disappeared (p = ns). However, the difference in α1 between the groups remained evident (p = 0.012) after adjusting for the above-mentioned covariates, indicating the role of both reduced vagal and increased sympathetic outflow among the patients.
Limitations
Uncontrolled factors such as the night-time sleep or other psychological and physiological stressors may contribute to daily HRV. Our subjects were voluntary consecutive patients or healthy controls scheduled to daily hospital routine, and we were not able to control the above-mentioned factors. In addition, we could not control the use of pain medications, which may have an effect on HRV. Even though we may be able to evaluate pain medications according to hospital databases, we do not know the quality and amount of over-the-counter pain medication. However, we believe that most of the patients used pain medication at least to some extent while control population did not. This should "dilute" the results as pain medication is supposed to alleviate pain symptoms. Unfortunately, we do not have knowledge about use of physical therapy but we do not regard it an important confounder as it (if it works) has similar effect as pain medication. However, we analysed the data when underlying co-morbidities were excluded and the results were the same. Obviously, subjects with co-morbidities use more likely medication than subjects without co-morbidities. Therefore, we feel that, at least to some extent, medication is taken into consideration.
Implications
Reduced HRV has been shown to be associated with the occurrence of various clinical events. Our results indicate that sciatica patients referred to spine surgery had autonomic dysregulation with decreased vagal activity and an increased sympathovagal balance compared with age-matched healthy controls. Therefore, it seems important to consider monitoring of the autonomic nervous system in addition to pain management in sciatica patients. We did not observe a significant relationship between impaired functional capacity caused by pain or pain intensity and HRV. In this respect, it can be suggested that HRV may reflect an independent intrinsic regulatory system of the autonomic nervous system that may be affected by the severity of the sciatic disease.