Introduction

Chronic low back pain (LBP) is one of the main causes of health problems resulting in disabilities, activity limitations, socioeconomic problems, and absenteeism from work worldwide [1]. Multiple factors including biopsychosocial condition influence transition from acute to chronic low back pain. Maladaptive movement and motor control disorders, central sensitization, fear avoidance behavior, and its effects on activity and participation are interrelated factors, forming a vicious cycle that influencing one and another [2]. This complexity results in low resolution of CLBP, counting less than 5% patient [3]. Multimodal treatment strategy by far is the most effective approach for chronic pain including pharmacology, non-pharmacology, and surgery. Strengthening exercises and core muscle stabilization are known to reduce pain and recurrence, while neuromotor training is effective in reducing the risk of injury and falls and improving several aspects of functional performance [4, 5]. Vagus nerve stimulation (VNS) is an electrical stimulation technique on the tenth cranial nerve afferents that has broad projections, can produce effects to the brainstem, sub-cortex, and cortex as well as the autonomic nervous system (ANS). Several studies have shown that VNS can be used for nociceptive modulation and pain perception [6]. Noninvasive form of VNS which is delivered by transcutaneous stimulation on auricular branch of vagus nerve (ABVN) has been shown advantages on anti-inflammatory effects and chronic pain comorbidities (depression, anxiety, and psychological factors) [7-10]. Thus, it supports therapeutic potency of tVNS in CLBP.

Chronic LBP research frequently evaluate pain and quality of life. However, pain and deconditioning have impact on functional ability that restricting patient’s activities and participation, limiting work and productivity. Functional capacity is an individual's ability to perform a task or action in a standardized environment, and it indicates the highest level of subject's functional ability that can be achieved in the domain being evaluated. Tests with specific instruments that can be selected to evaluate the patient's functional capacity include the sit-to-stand test and the timed up and go test [11]. Functional mobility is important to assess because it shows the ability to carry out daily activities and plays a role in maintaining an active lifestyle, while sitting to standing is a prerequisite movement to perform functional mobility.

Five times sit to stand test (FTSST) is used to evaluate lower extremity muscle strength and balance, where LBP patients show lower performance on FTSST than healthy subjects [12, 13]. Timed Up and Go Test (TUG) is used to evaluate fall risk, balance, and functional mobility [14, 15], where LBP patients show reduced functional mobility and worse results than healthy subject [16]. Both tests are mentioned to have strong to moderate correlation with the pain scale in CLBP [17-19]. Studies on the effects of tVNS on chronic low back pain with functional capacity as a result have not been obtained. This study aims to determine the effect of adding tVNS therapy to exercise as mainstay therapy to chronic low back pain on the functional mobility and lower extremity strength of chronic low back pain patients.

Materials and Methods

Study design and procedures

This was a randomized controlled group study. Participants were consecutively selected in order of their appearance according to inclusion criteria up to number of participants were fulfilled. Based on sample calculation, 22 enrolled participants were randomly assigned to experimental group and control. The study was approved by ethic committee of Dr. Soetomo general academic hospital in Surabaya. Two physicians collected the demographic data, basic anthropometric measurement, history of mechanical CLBP, and clinical symptoms prior to randomization.

Eligibility

Inclusion criteria

Participants aged 18-55 years old with mechanical chronic low back pain (defined as LBP more than 12 weeks without organic signs and red flags), moderate pain with numerical pain rating scale between 4 and 7, and independent ambulation.

Exclusion criteria

Excluded were patients with organic LBP (trauma/fracture, tumor, infection, severe degenerative spine, and rheumatologic condition), radicular pain, analgesic consumption other than acetaminophen or NSAID, or new analgesics in 2 weeks before recruitment, underwent modalities therapy in 1 week, any injury or skin problems at auricula or face, utility of metal implant including pacemaker, pregnancy, history of seizure or epilepsy, moderate to severe depression (HDRS score ≥ 17), history of vasovagal syncope, skin allergy to metal, drugs and alcohol abuse, communication problem, obesity grade 2 according to Asia Pacific criteria, and diabetes mellitus type 2. The criteria were dropped out if participants missed stimulation schedule or exercise twice, experienced allergy, or adverse event.

Stimulation procedure

Participants in experimental group received tVNS administered by researcher. The tVNS treatment lasted 20 minutes per day and exercise session lasted 30 minutes per day. tVNS was applied to left ear at cymba choncha and choncha area using ear clip electrodes connected to Enraf-Nonius Myomed 632 device.

Conductive gel applied to metal part of electrodes to distributes conduction and prevent pain. Stimulation set to 25 Hz and pulse width 500 microseconds, in biphasic rectangular symmetric waveform. The intensity adjusted to every participant’s sensory threshold by questioning the tingling sensation without pain. Stimulation was delivered 20 minutes, five times per week for 2 weeks, accompanied by monitoring of vital signs (blood pressure, heart rate, respiratory rate, and peripheral oxygen saturation) before, every 5 minutes during, and after 30 minutes stimulation ended.

Participants were asked to report any complain of increasing pain or discomfort sensation. After stimulation was finished, researcher checked area of treatment for any signs of irritation and evaluate participant’s symptoms.

Exercise treatment

All participants in both groups participated in exercise therapy under the blind supervision of an experienced physiotherapist. Exercise treatment consisted of kinesthetic awareness of spinal posture, pelvic tilt exercise, diaphragmatic breathing, core strengthening exercise using abdominal drawing in cat and camel exercise, trunk flexibility training, administered twice a week, 30 minutes per session for two weeks.

Outcome

Outcome variables are lower extremity strength function measured by five times sit to stand test (FTSST) and functional mobility measured by Timed Up and Go Test (TUG). The outcomes were evaluated before and after two weeks of intervention. To measure FTSST, a hard seat chair 43 cm high is used. In the initial position, the patient is asked to sit with his arms crossed on his chest. Next, the patient is asked to stand and sit five times as quickly as possible [20, 21]. Cut off point to differentiate participant with or without objective functional impairment is 10.35 [22]. Functional mobility is the term used to denote balance and walking maneuvers used in everyday life (such as getting up from a chair, walking, and turning) [23]. The test is carried out by measuring the time needed by the participant to transfer from a sitting position to standing then walking as fast as possible, but not running as far as 3 meters, turning around and sitting back down [21]. Time needed to finish test was considered normal without the risk of fall if scored 10 [2]. Factors influencing TUG result are motor deficit, age, sex, body mass index, comorbidity (cardiorespiratory comorbidity), and psychological condition (i.e. motivation) [17].

Statistical analysis

In this study, IBM SPSS Statistics 23.0 and Microsoft Excel for Mac version 16.68 were used for statistical analysis and calculation. Paired t- test analysis was used to compare FTSST and TUG score pre-test and post-test within group, an independent t-test was used to compare scores between groups. P-value <0.05 is considered significant. Cohen’s d calculation was also used to measure effect size of therapy.

Results and Discussion

Baseline characteristics of participants in variables of age, sex, body weight, body height, body mass index (BMI), pretest score for numerical pain rating scale (NPRS), Hamilton depression rating scale (HDRS), FTSST, and TUG pre-intervention are presented in Table 1. CLBP improvement was known to be affected by confounding factors, in terms of BMI and depression [24]. Thus, no significant difference was found between control group and experimental group in baseline variables.

Score presented as ¹percentage and ²mean ± standard deviation. P-value based on ¹Chi-square test and ²independent t-test. *Significant if p-value < 0.05. BMI: Body Mass Index; NPRS: Numerical Pain Rating Scale; and HDRS: Hamilton Depression Rating Scale. As presented in Table 2, experimental group had an average FTSST time before being given tVNS therapy of 18.06 ± 9.20 seconds, and the mean after being given tVNS therapy was 12.33 ± 2.42 seconds. Based on the parametric statistical test (paired t-test), there was significant improvement in the FTSST time in the experimental group (p-value = 0.039). In the control group, the average FTSST time at the initial assessment was 12.12 ± 4.05 seconds and the average at the final evaluation was 12.17 ± 3.01 seconds. Based on the parametric test (paired t-test), there was no significant improvement in the FTSST time in the control group (p-value = 0.945).

In TUG evaluation, average TUG of the experimental group before therapy was 10.13 ± 2.68 seconds, and after tVNS therapy was 7.76 ± 1.46 seconds. Based on the parametric statistical test (paired t-test), there was a significant improvement in TUG of experimental group (p-value = 0.011). In control group, the average TUG time at the initial assessment was 9.23 ± 2.00 seconds and the average at the final evaluation was 8.71 ± 3.13 seconds.

Based on the parametric test (Paired t-test), there was no significant improvement in TUG in the control group (p-value = 0.553). The difference (delta) of 5 times sits to stand (FTSST) and the timed up and go test (TUG) between the experimental group and the control group is indicated in Table 3.

Table 1: Patient characteristics at baseline

Table 2: Five Times Sit to Stand (FTSST) and Timed Up and Go Test (TUG) of both groups before and after intervention

As provided in Table 3, the mean delta time of the FTSST experimental group was 5.73 ± 7.98 seconds, while the control group was 1.74 ± 1.47 seconds, means that there was no significant difference of FTSST time between groups (p-value = 0.119). The effect size was calculated by Cohen's d, with result of experimental group was 0.85, indicated that therapy in the experimental group had a large effect on improving the FTSST time, while the result in the control group was 0.01 indicating that therapy in the control group had a weak effect on improving the FTSST time. The mean TUG time delta for the experimental group was 2.38 ± 2.50 seconds, while the control group was 0.52 ± 2.82 seconds. Based on the independent t-test statistical test, there was no significant difference between the TUG time improvements between groups (p-value = 0.117). The effect size was calculated by Cohen's d, resulting in effect size of the experimental group was 1.09, indicated that therapy in the treatment group had a large effect on improving TUG time, while the effect size in the control group was 0.19 indicating that therapy in the control group had a weak effect on improving TUG time. In application of tVNS stimulation, there was no reported side effect. All of the patient enrolled finish the treatment. Figure 1 displays the comparative data of FTSST pre- and post-intervention in box and whisker plot between the two groups. With the pre-intervention data showed higher plot distribution of experimental group, the post- intervention data showed smaller range, skewed to the left side and larger differences between pre- and post- intervention of experimental group.

In Figure 2, comparative data of TUG before and after treatment between the two groups shown that the experimental group pre intervention has larger range value, post-intervention data showed shorter range and smaller distribution, suggest larger differences between them compared to the control group.

This is the first study to evaluate tVNS addition to exercise therapy effects on physical function of CLBP patient in Indonesia. In CLBP patients, pain is the most frequent outcome used in studies. Several studies state that the outcome of functional capacity is affected by the pain scale, as shown by the correlation between the pain scale, FTSST, and TUG [15, 19]. Concerning non-physiological factors (psychological and environmental) that impact on the result of physical performance [25], our study further evaluated depression scale of the participants with the result of HDRS showed no significant difference between groups. The results showed significant improvement of lower extremity strength in experimental group compared to baseline (p<0.05). In terms of the minimal clinically important difference (MCID) value of the FTSST range from -5 to -7 [26], there was a mean difference of 5.73 ± 7.98 in experimental group, indicating clinically significant improvement, while in the control group, with a mean difference of 1.74 ± 1.47, did not. Previous study combining tVNS and physical therapy for fibromyalgia patient did not show improvement in 30 times sit to stand test that was evaluated at the 6^th and the12^th weeks after intervention, although pain scale improvement was obtained [19]. This study has similarities in combination therapy and outcome. However, the different subject, stimulation dose, duration, exercise type, and additional acupuncture therapy made difficult comparison. Other analgesic study without exercise therapy for 2 weeks also fail to show improvement in function, suggest that although a significant decrease in pain scale was obtained, it did not necessarily improve the subject's functional abilities [27]. Functional abilities also being influenced by other factors namely motor control, strength and stabilization, sensory feedback, postural control, coordination, and balance that developed through physical exercise [28, 29]. The mechanism that causes significant improvement in the experimental group given additional tVNS therapy is unclear, but it is thought to be obtained from tVNS mechanism of action which provides analgesics, anti-inflammatory effects, and psychological improvements, namely depression and mood [10, 30-33].

Table 3: The difference (delta) of 5 times sit to stand (FTSST) and the timed up and go test (TUG) between the experimental group and the control group

Figure 1: Box and whisker plot diagram of five times sit to stand test (FTSST) pre-and post-intervention between the two groups. Light grey box showed pre-test measurement and dark grey box showed post-intervention

Figure 2: Box and whisker plot diagram of timed up and go test (TUG) pre- and post-intervention between the two groups. Light grey box showed pre-test measurement, and dark grey box showed post- intervention

The effect of VNS on pain scale of patients with chronic LBP supports this study result. The tVNS study in Indonesia on CLBP showed significant improvement of pain scale in both the tVNS group and exercise [34]. Similar results showed by other studies conducted by Sator-Katzenschlager [35]. The results of this study indicated that there was a significant improvement in the TUG of the experimental group who received exercise therapy plus TVNS before and after the intervention (p=0.011). In terms of the minimal clinically important difference in chronic LBP of 2.1 seconds [36], the treatment group obtained a mean difference of 2.38 ± 2.50, which means that there was clinical improvement in TUG, while control group mean difference was 0.52 ± 2.82 means no clinical improvement. Although no significant difference found in TUG results between groups, the effect size value in the experimental group was 1.09 indicating a large effect on improving TUG, and an effect size of 0.19 indicated a weak effect in the control group. There have been no studies regarding tVNS in chronic LBP patients with TUG outcomes, so comparisons are difficult to make. Improvement in TUG of experimental group probably because decreased pain mechanism. This is supported by several studies state that showed strong to moderate correlation between TUG and VAS [17]. Previous studies investigated tVNS on TUG and gait speed in Parkinson’s disease resulting in improvement of gait speed and motor function with suspected mechanism from indirect effect on brain cholinergic system that induce neuromodulation. This interesting result could also be the mechanism contribute to improvement in TUG, considering maladaptive cortical reorganization that occur in CLBP, and tVNS ability to induce neuroplasticity shown as cortical motor reorganization [37, 38]. The non-significant difference results between the two groups probably because exercise therapy has provided a relatively small effect to improve outcomes although inadequately pass threshold of meaningful difference due to relatively short-term treatment.

Meanwhile, tVNS adjunctive therapy added the effects so that the results exceeded the threshold which could be seen statistically significant. The small effects resulted from exercise is likely because of the short period of intervention as only two weeks, that inadequately obtain positive outcome in function. Previous study showed significant improvement in FTSST in longer periods after 6 weeks and 12 weeks of aerobic and core stability exercise [12] while TUG after 8 and 12 weeks of exercise treatment [39, 40]. This is supported by a study investigated responsiveness of TUG to minimal change that could be detected in 2 weeks after multidiscipline treatment in frail patient supports the result of the current study [41-44]. Furthermore, diagram box and whisker plot skewness to the left showed us a trend of data to smaller value, which means tendency of improvement in the result test.

Conclusion

As growing evidence supports the beneficial effects of tVNS in chronic pain, this study supports the potency on its effects to functional capacity in terms of functional mobility and lower extremity strength of CLBP patient in relatively short term of two weeks therapy, also its safety and effectivity. Further investigation in larger study would needed to confirm this potential effect.

Acknowledgements

The authors would like to thank Patricia Maria Kurniawati, MD for her contribution in research preparation.

Disclosure Statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' Contributions

All authors contributed to data analysis, drafting, and revising of the paper and agreed to be responsible for all the aspects of this work.

Orcid

Retno Nirmala Kusumastuti

https://orcid.org/0009-0006-7198-2349

I Putu Alit Pawana

https://orcid.org/0000-0002-6775-964X

Yudith Dian Prawitri

https://orcid.org/0000-0002-6880-4262

Soenarnatalina Melaniani

https://orcid.org/0000-0002-4449-153X

HOW TO CITE THIS ARTICLE

Retno Nirmala Kusumastuti^*, I Putu Alit Pawana, Yudith Dian Prawitri, Soenarnatalina Melaniani, The Effects of Transcutaneous Auricular Vagus Nerve Stimulation and Exercise on Functional Capacity of Chronic Low Back Pain. J. Med. Chem. Sci., 2023, 6(12) 2974-2984.

DOI: https://doi.org/10.26655/JMCHEMSCI.2023.12.12

URL: https://www.jmchemsci.com/article_177071.html