The combined effect of neuro-modulation and neuro-stimulation on pain in patients with cervical radiculopathy – a double-blinded, two-arm parallel randomized controlled trial

Abstract

Introduction

Cervical radiculopathy is one of those disabling conditions which results in central and peripheral pain and thus affects the quality of life. Transcutaneous Electrical Nerve Stimulation (TENS) and exercises produce analgesic effect but their long-term effect has not been available to date. Transcranial Direct Current stimulation (tDCS) is known to produce promising effects on central pain by targeting cortical activity.

Purpose

To determine the combined effect of tDCS and TENS with exercises on pain and quality of life in patients with cervical radiculopathy.

Method

Forty four patients (male: female = 26:18) of the age group 18–50 years were recruited and randomly allocated into the experimental group and control group. The experimental group received active anodal tDCS for 20 min with an intensity of 2 mA, while the control group received sham anodal tDCS. TENS over the pain distribution area for 20 min with 5 Hz intensity and 80-150 ms pulse duration followed by neck-specific exercises were given in both groups. This protocol was given 5 days a week for 4 weeks. Pre and post-assessments were obtained through outcome measures that the Numeric Pain Rating Scale and Neck Disability Index for the measurement of pain, functional disability, and quality of life.

Result

Paired t-test/Wilcoxon-Signed Rank test, and Index and Mann–Whitney U test were used to compare the demographic variables within and across the groups, respectively for Neck Disability for Numeric Pain Rating Scale, keeping the P-value < 0.05 as significant. One-way repeated-measures analysis of variance (ANOVA) was applied to determine the between-subject factor differences. Post hoc tests with Bonferroni correction for repeated analyses were performed. Results depicted a significant effect for NDI (P = 0.001 for both groups) and NPRS (P = 0.003 for the experimental group and 0.007 for the control group). Significant Interaction effect (time*group) was observed for NDI (F = 42, 5382.77) and NPRS (F = 42, 1844.57) with a P-value of 0.001 for both outcome measures. Clinical significance was observed for both outcome measures having a mean difference in 50.21 and 4.57 for NDI and NPRS, respectively compared with the established MCID of 13.2 and 2.2 scores for respective outcome measures.

Conclusion

It was concluded that active tDCS along with TENS and exercise intervention was effective on pain, disability, and quality of life in patients with cervical radiculopathy.

Introduction

Cervical radiculopathy (CR) is the most common compressive focal neuropathy (1). In the general population, the prevalence rate of CR is 83.2/100,000 patients. The common age group affected by CR is 13–91 years (2). The prevalence was the highest in middle-aged adults suffering from cervical radiculopathy and the chronicity of the symptoms is evident to be increasing with advancing age (3, 4). It is a type of sensorimotor deficit that leads to several functional disabilities and affects the quality of life of patients (5). Evidence suggests that lower levels of the cervical spine produce a maximum range of flexion and extension, and are subjected to higher loads hence C5-C6 and C6-C7 levels are the common levels which undergo degeneration and compression. Therefore, anatomical changes also account for the higher incidence of CR (1). Clinical evaluation is one of the most reliable methods to diagnose CR, however, MRI and Electromyography are important tools (6). Various tests can be performed to confirm nerve involvement, among which the upper limb tension test (ULTT) is the most sensitive test and can be used as a screening tool (7).

Pharmacological and surgical management has numerous limitations and side effects (1, 8) in comparison to manual therapy which has its benefits and good impact on symptoms (9). But in chronic conditions, there is a formation of pain memory and it is difficult to cure with only conventional methods (10). The ability to recall past pain experiences is the concept of pain memory which is a characteristic found in psychological theories that aim to elucidate how individuals perceive and respond to acute pain, as well as how patterns of chronic pain behavior develop (11, 12). Conventional methods used to treat chronic pain include electrotherapeutic modalities such as Transcutaneous Electrical Nerve Stimulation (TENS) and Interferential Therapy (IFT), exercise therapy, and manual therapy (8). There is no known therapy aimed at pain memory mechanisms associated with neuropathic and chronic pain conditions such as persistence and sensitization. Numerous pieces of evidence suggest that interventions for alleviating neuropathic pain primarily focus on the cortex without effectively addressing the specific local areas involved (8, 13). Transcutaneous Electrical Nerve Stimulation (TENS) is a non-invasive and non-pharmacologic neuro-stimulatory modality for reducing pain. The effectiveness of TENS for pain relief has been shown in several clinical studies. It acts via central and peripheral mechanisms to reduce pain (10, 13). It is also evident that Neck Specific Exercises (NSE) are effective in strengthening the deep muscle of the cervical spine and have a good impact on pain and radicular sensation (14).

Neuromodulation is a technique to target the cortex to stimulate or inhibit the activity of the targeted area of the cerebral cortex and results in neuroplastic changes (15). Transcranial Direct Current Stimulation (tDCS) is a non-invasive technique designed for clinical use, aiming to regulate brain activity by employing sizeable electrodes placed on the scalp over the specific targeted brain area. This method involves delivering a gentle and constant current to the brain (16). Anode stimulation of the M1 motor cortex area alters the activity of the cortico-thalamic pathway and is an accepted strategy for treating neuropathic pain (17, 18).

Chronicity of radiating pain can contribute to a shift from the peripheral level to the central level by processing pain signals, making the experience of pain more intense and widespread (19, 20). Therefore, the purpose of this study was to evaluate whether targeting both the central (via tDCS) and the peripheral nervous system (via TENS) leads to increased pain relief, decreased functional disability, and improved quality of life compared with targeting only the peripheral nervous system in patients with cervical radiculopathy. To the best of the authors’ knowledge, there is no such evidence that claim to target the nervous systems and the musculoskeletal system. Hence, the study aimed to provide evidence on the combined effect of tDCS and TENS with exercises to reduce pain and functional disability and improve the quality of life in patients with cervical radiculopathy.

Material and methods

This was a two-group pre-test post-test randomized clinical trial. Ethical clearance was obtained from the Institutional Research Ethics Committee of a tertiary care teaching hospital (IEC-1471). This trial was performed from September 2019 to October 2020 and the study was registered under the Clinical Trial Registry with registration number CTRI/2019/09/021208. The study strictly followed the standard ethical principles adopted by the World Medical Association which include the medical research involving human patients, the Helsinki Declaration, Revised 2013, and the ethical guidelines adopted by the Council for International Organizations of Medical Sciences (CIOMS), the International ethical guidelines for health-related research involving humans (Revised, 2016). The study also adopted the ethical guidelines that followed the National Ethical Guidelines for Biomedical and Health Research Involving Human Participants 2017.

Sample size estimation

A priori type of power analysis was done to estimate the sample size with the help of G*Power software, version 3.1.9.7, released in April 2020, by using an effect size of 1.67 from a previous study conducted by Nihal et al. in 2018 (17). The statistical test used was “Means: Difference between two independent means (two groups)”. The power of the study was 0.95 and 0.05 was taken as a level of significance. Allocation ratio N2/N1 was set as 1. It comes out to be n = 44 (22 patients per group).

Selection criteria

For both sexes, aged between 18–50 years with unilateral upper limb pain radiating in the lateral aspect of the arm, forearm and hand for at least 3 months, the Neck Disability Index (NDI) score should be up to 60% along with Numeric Pain Rating Scale (NPRS) score > 6 and positive upper limb tension test for median nerve (ULTT1) were recruited for the study. Patients with a history of injury to the cervical spine, patients who underwent cervicothoracic spine surgery, bilateral symptoms, upper motor neuron impairments, use of steroids and pharmacological therapy, and any congenital anomaly like cervical rib, were excluded. Written informed consent was taken from the participants before the study. The detailed study plan was explained to the participants.

Recruitment

Forty four participants aged, 18–50 years old, were recruited via informed consent from the out-patient department of a recognized super-specialty hospital for this randomized controlled trial.

Randomization, allocation, and blinding

After the baseline assessment, the participants were randomly allocated to either the control group or the experimental group. The randomization sequence was created using the lottery method, a simple randomization method. The allocation sequence was concealed from the researcher, enrolling and assessing participants in sequentially numbered, opaque, sealed, and stapled envelopes. Participants along with outcome assessors and data analysts were blinded to the procedure. The study flowchart has been followed as per Consolidated Standards of Reporting Trials (CONSORT) guidelines. (Fig. 1)

Figure 1.

Modified CONSORT flow diagram of the study.

Study procedure and outcome measures

Preliminary examination was done on baseline to evaluate pain perception in patients with cervical radiculopathy. The entire demographic characteristics, such as age, sex, weight, and height, were recorded. Each participant was assessed for pain, functional disability, quality of life, nerve sensitivity, and sensory involvement by using Numeric Pain Rating Scale (NPRS), Neck Disability Index (NDI), Upper Limb Tension Test (ULTT) 1, sensitive for median nerve and anterior interosseous nerve, respectively. A Neck Spurling test was also performed before ULTT to check the nerve involvement by pain provocation. All these procedures take about 30 min. A written informed consent form was obtained from all the participants for their voluntary participation.

Outcome measures

Numeric Pain Rating Scale (NPRS)

It is a valid and reliable scale used to measure pain with an Intraclass Correlation Coefficient (ICC = 0.67). There are 11 components in total, with a scoring range from 0 to 10, where 0 signifies the absence of pain, and 10 indicates the highest level of pain. Patients are required to indicate the number that most accurately reflects their current pain level (21, 22).

Neck Disability Index (NDI)

It consists of a series of questions related to various activities, and the patient rates their level of difficulty in performing each activity on a scale from 0 to 5 where grade 0 represents no to negligible symptoms and grade 5 represents severe symptoms. The total score is then calculated and converted into a percentage with higher scores indicating greater disability and limitations due to neck pain. 0-20% indicates normal condition, 21-40% indicates mild disability, 41-60% indicates moderate disability, 61-80% indicates severe disability, and more than 80% indicates exaggerated disability. NDI showed excellent reliability (ICC = 0.88) (22).

Treatment procedure

The experimental group received a combination of active tDCS (2 mA) and TENS (80-150 ms) for 20 min. After that patient underwent exercise intervention under the supervision of a therapist. In the control group, sham-tDCS was administered, using the same placement of tDCS electrodes as in the experimental group. However, in this case, the electrical current was activated for only 2 min and then promptly deactivated. This was administered in conjunction with TENS and followed the same exercise intervention parameters as those applied in the experimental group. The protocol was given for 5 days a week for 4 weeks.

Transcranial direct current stimulation (Walnut Medical, India)

10/20 EEG electrode placement system is a reliable and valid method to measure the target area because it is individualized to each patient’s head size and shape (23, 24). The steps for placing the electrodes of tDCS have been explained in Fig. 2. This method is more reliable compared to the EEG cap because that has a fixed point for each electrode placement (25). The placement of electrodes was decided on the basis of the extremity involved. If the right extremity was targeted, then electrode placement was C3 and Fp2. If the left extremity was targeted, then electrode placement was C4 and Fp1. A constant current of low amplitude (2 mA) was supplied across the scalp of the patient for 20 min. Any kind of abnormal or itchy sensation was asked to be reported immediately (17, 26).

Figure 2.

10/20 EEG electrodes positioning for tDCS.

TENS (Ntech Medical Systems, India)

To relieve peripheral radiating pain, conventional TENS of high frequency (80 Hz), low intensity (as per the patient’s comfort but should not be painful and not elicit the muscle contraction) and a pulse width of 150 µs of asymmetrical biphasic rectangular waveforms, has been used for 20 min. Electrodes were applied in the dermatomal pattern of the radiating pain i.e. two electrodes were applied at the neck area at the C7 vertebra and scapular blade, and the other two electrodes were placed on the anterior aspect of the arm at the upper and lower ends, respectively, then another set of electrodes was positioned at the anterior aspect of the forearm where one electrode was placed at the belly of Pronator Teres muscle and another electrode was placed at the belly of Flexor Digitorum Profundus muscle (27).

Exercise intervention program

The patient was asked to lie down in a supine position keeping the neck in a neutral position by placing a folded towel under the occiput and the therapist sitting at the head side of the patient. The procedure was thoroughly explained to the patient. Instruction was given to press the towel by occiput and simultaneously perform chin depression. The patient should apply only 10% pressure on the head and hold the position for 10 seconds and after that neck should be relaxed with expiration. It should be held for 10 s with 10 repetitions twice a day. In the same position, the patient applies resistance over the temporal area bilaterally performs isometric rotation of the neck and repeats this exercise 10 times on each side with the same intensity and frequency as the previous exercise. An active range of motion of the neck is performed for each movement. Flexion, extension, lateral flexion, and rotation with 10 repetitions twice a day (28, 29).

ULTT 1

This test is sensitive for the median nerve and anterior interosseous nerve with root values C5, C6, and C7. The patient was in the supine position and the examiner stood in a walk stance position on the side to be tested facing toward the patient. The shoulder was abducted for about 110° and was then depressed by the other hand. Then the elbow was extended keeping the forearm in supination with the thumb and finger in extension. After that opposite side lateral neck flexion was added to check the sensitivity (30).

Data analysis

The data were analyzed using statistical software, SPSS 20 (Statistical Package for Social Sciences version 20 SPSS Inc. Chicago, IL, USA.). The distribution of data was assessed using the Shapiro–Wilk test. Comparison of demographic variables was done across groups with the help of an Independent sample t-test for the Neck Disability Index and Mann–Whitney U test for the Numeric Pain Rating Scale. A P-value of >0.05 was indicative of statistical significance, depicting normal distribution. A paired t-test and Wilcoxon-Signed Rank test were used to analyze the within-group differences for NDI and NPRS, respectively, keeping the P-value < 0.05 as significant. One-way repeated-measures analysis of variance (ANOVA) was applied to determine the between-subject factor differences, significant level, and Observed Power obtained for the outcomes. Post hoc tests with Bonferroni correction for repeated analyses were performed. A significance level of P < 0.05 was adopted for all comparisons.

Results

Recruitment and general characteristics of the participants

A total of 44 participants were recruited for the study, with 22 participants randomized to each of the experimental and control groups. The baseline characteristics of both groups were similar with the number of males more than that of females. Participants in both groups complained of pain for more than 3 months with an average duration of 3.69 and 3.81 months, respectively. The dominant hand was found to be more affected than that of the non-dominant hand in both groups. There was no significant difference in pre-assessment measures of NDI and NPRS (Table 1).

Table 1.

Demographic Characteristics and baseline measurements for all the variables.

Demographic Characteristics [Mean (95% CI)]	Experimental Group (n = 22)	Control Group (n = 22)	P-value
Sex (M/F)	n = 12/10	n = 14/8	-
Age (in years)	39.11 (30.05–48.18)	41.89 (36.12–47.66)	0.04# *
Duration of radiating pain (Months)	3.69 (3.31–4.06)	3.81 (3.38–4.23)	0.63#
Arm length (cm)	60.67 (53.49–67.85)	58.11 (52.08–64.15)	0.49#
Side affected (dominant/ non-dominant)	n = 15/7	n = 16/6	-
Baseline Variables NDI [Mean (95% CI)]
NDI	78.75 (75.31-82.20)	79.67 (76.64-82.69)	0.67#
NPRS Score§ [Median (min-max)]
NPRS	8 (7–9)	8 (7–8)	0.55§

Abbreviations: NPRS- Numeric Pain Rating Scale; NDI- Neck Disability Index; CI- Confidence Interval; cm- centimeter; M/F: Male/Female, cm-centimeters, min: minimum, max: maximum.

^#: Independent t-test, ^§: Mann-Whitney U test. *^: P-value < 0.05 (not comparable at baseline).

Quality of life (NDI score)

After 4 weeks of intervention, quality of life was assessed using NDI scores which were calculated in percentage. Within-group analysis depicted significant improvement in both groups (P-value = 0.001). A between-group comparison was made using the time*group interaction effect which showed significant improvement in the experimental group (P-value = 0.001) and F = (42, 5382.77). It also gained an extremely large effect size (partial eta squared = 0.997) with an observed power of 100%. (Table 2)

Table 2.

Group comparison of all the variables for both groups.

Variables	Experimental group (n = 22)			Control group (n = 22)			Between Group
NDI
	Pre- Mean (SEM)	Post-Mean (SEM)	P-value	Pre Mean (SEM)	Post Mean (SEM)	P-value	Mean Difference (95% CI)	Interaction effect (Time*Group)	P-value	Partial eta squared	Observed Power
NDI	78.75 (1.54)	22.85 (1.49)	0.001*	79.67 (1.31)	35.33 (0.94)	0.001*	50.21 (48.83-51.59)	F = (42, 5382.77)	0.001#	0.992	1.00
NPRS
	Pre-Median (IQR)	Post-Median (IQR)	P-value	Pre- Median (IQR)	Post-Median (IQR)	P-value	Mean Difference (95% CI)	Interaction effect (Time*Group)	P-value	Partial eta squared	Observed Power
NPRS	8.0 (7.0-8.0)	3.0 (2.0-3.0)	0.003§	8.0 (7.5-8.0)	4.0 (3.5-4.0)	0.007§	4.57 (4.35-4.78)	F = (42, 1844.57)	0.001#	0.978	1.00

Abbreviations: NPRS- Numeric Pain Rating Scale; NDI- Neck Disability Index; CI- Confidence Interval; SEM- Standard Error of Mean; IQR- Interquartile Range.

^#:Two-way ANOVA, *Paired t-test, ^§Wilcoxon Signed Rank test

The level of Significance (P-value) was set at < 0.05.

Pain (NPRS)

Pain scores were compared using NPRS. As NPRS is a discrete variable, the result has been expressed in the median and interquartile range. The within-group analysis exhibited significant differences for both groups with P-values of 0.003 and 0.007 for experimental and control groups, respectively. The between-group analysis depicted significant improvement in the experimental group (P-value = 0.001), F = (42, 1844.57) and large effect size (0.978). The power observed for the outcome was 100%. (Table 2)

Time*group interaction for both outcomes i.e. NDI and NPRS was represented as Estimated Marginal Means in Fig. 3 and Fig. 4, respectively.

Figure 3.

Estimated Marginal means of quality of life scores.

Figure 4.

Estimated Marginal means of pain scores.

Discussion

In this study, it was concluded that the effect of transcranial direct current stimulation in combination with transcutaneous electrical nerve stimulation and exercise intervention has a good impact on reducing pain and enhancing the quality of life of patients with cervical radiculopathy.

In cervical radiculopathy, the musculoskeletal system also gets affected along with the neural component. That’s why exercise intervention is an effective approach in stabilizing the spine, relieving some extra pressure from the nerves, reducing inflammation on microglial cells, and modulating neuronal activity (28, 31). Deep neck flexor strengthening has been effective in the literature (31). Marie et al. work on patients with CR to establish the short- and long-term effects of exercise intervention. They found a significant effect on (p = <0.05) neck flexor endurance after completion of a 14-week protocol and after 12 months of follow-up (29). Another review with meta-analysis to check the effect of exercise on cervical radiculopathy shows a significant effect of exercise therapy with and without another treatment approach (30).

The result indicates that there was a significant improvement in group 1 which received active tDCS, TENS along exercise intervention in comparison to group 2 in outcome measures NDI, NPRS, and ULTT. As per evidence, these tools are quite appropriate to assess major aspects of the condition for instance, disability (30), quality of life (32), pain (33), and nerve involvement (34). The result is further substantiated by the effect size determined in the current study using Cohen's d formula, yielding a value of 0.34 for NDI in the experimental group, indicating a moderate effect. Additionally, the study's power, as determined through post hoc analysis, is statistically significant given the sample size. MCID value of NPRS (2.2) (22, 33) and NDI (8.5) (22, 32, 33), and MDC value of NDI (13.4 for cervical radiculopathy), are through which the clinical significance of the study has also been established. Standard Error of Measurement (SEM) is 5.7 with the age of 49 ± 9.7 years in 165 participants with cervical radiculopathy. The reliability and validity of ULTT were established in the literature on peripheral neuropathic pain (34, 35). The clinical significance was exhibited for both outcome measures as the mean difference was 50.21 for NDI and 4.57 for NPRS which are more than that of established MCID of the outcome measures.

In the literature, it has been stated that NDI is only used for the assessment of disability but it is also evident that there is a strong correlation between NDI and other quality of life (QoL) measures such as 3rd level of European Quality of Life in Five Dimension (EQ-5D-3L), The 36-items Short Form Health Survey questionnaire (SF-36) with a level of significance <0.001 (36, 37). In this study, we use NDI as a tool to measure quality of life along with functional disability.

Research established the isolated effects of tDCS, TENS, and exercise intervention in various neuropathic pain conditions such as post-spinal cord injury (SCI) (16, 38, 39), phantom limb pain (PLP) (40, 41), lumbar radiculopathy (42), and cervical radiculopathy (27). In some literature, a combination of two approaches was given to the patients to relieve their symptoms e.g. tDCS and BreEStim in patients with neuropathic pain after SCI (38), tDCS with the postural training in patient lumbar radiculopathy (42) and TENS with cervical traction in cervical radiculopathy (27). In these studies, all treatment methods and combinations of treatments demonstrated a moderate to substantial positive impact on improving the patient’s condition.

As per the results of the present study, there is a difference between the groups after completing the treatment protocol. Patients of the experimental group showed significant improvement after the treatment compared to the control group. After observation and analysis of the post-intervention scores for NPRS and NDI, it became evident that there was a significant decrease in the patient’s pain levels and functional disability. This improvement was accompanied by an enhancement in their overall quality of life, particularly among those who received active tDCS.

Within-group differences were seen in both experimental and control groups but between-group analysis showed a more significant effect in the experimental group compared to the control group. After the analysis, it can be concluded that sham tDCS doesn’t provide any positive effect on reducing pain and improving quality of life among patients with cervical radiculopathy as there were no physiological changes through the placebo effect. So we concluded that in the control group, TENS and exercise intervention mainly produced the desired effect. The theory behind the stimulation of the motor cortex (M1) with active anodal stimulation is that M1 stimulation alters the activity of the cortico-thalamic pathway to reduce pain perception (38, 43, 44).

According to recent literature, it has been proven that the tDCS is an appropriate choice of treatment for chronic pain. Because it modulates neuronal activity spontaneously and shows the neuroplastic changes that lead to the long-lasting effect of treatment. A review with meta-analysis article included approximately 60 studies to prove the result (26, 43, 45).

Eun et al. found the effect of active vs. sham tDCS on 16 patients with spinal cord injury having chronic neuropathic pain. They used the same parameters of tDCS as the current study 2 mA, 20 min. session. The effect of treatment is observedthrough the pre- and post-functional imaging (PET-MRI). They found significant metabolic changes in the brain area after the end of the session. The main physiology behind the action of cortical stimulation by direct current is NMDA-mediated neuroplasticity in the synaptic zone (39, 44).

To the best of our knowledge, there is a lack of existing evidence that specifically addresses the modulation of pain and neuropathic symptoms by targeting both central and peripheral pain pathways simultaneously. In the current study, we targeted both central and peripheral pain pathways to modulate neuropathic pain and thereby its sensory symptoms. In this study, the exercise intervention may also help to improve the maladaptive changes in the brain resulting because of chronic neuropathic pain, by enhancing the neuroplasticity and by providing stabilization to the cervical spine (9, 28–31). Although a randomized clinical trial determined that the technique helps to open the intervertebral foramen it was not able to prove its hypothesis (45).

A critical review established that the tDCS is having a moderate effect on neuropathic pain (SCI) (43). Another study also indicated that neuropathic pain lasting for an extended duration, such as more than five years, tends to be less responsive to tDCS treatment, demonstrating a refractory nature (17). In a few studies, the primary motor cortex (C3, C4) is the most reliable area of stimulation to alter neuropathic pain. Choosing a motor area for pain inhibition is thought to inhibit the activity of cortico-thalamic tracts (17, 18, 46). But in another study, the dorsolateral prefrontal cortex is also used for pain but motor cortex stimulation helps to alter the pain perception as well as sensory tolerance (47). That’s why it is the most reliable method to treat the pain. It has also been reviewed in the literature the treatment effect does not fade away with time because the impacts of tDCS vary based on polarity. These effects persist above their baseline levels for up to an hour following a single tDCS session. Prolonged adaptations seem to be influenced by the strengthening or weakening of synaptic activity, which relies on the activation of the glutamatergic NMDA (N-methyl-D-aspartate) receptor (48, 49). Depending on the specific stimulation parameters, tDCS can bring about changes in distant areas by effectively adjusting interconnected networks. Functional neuroimaging has revealed that tDCS-induced alterations in regional cerebral blood flow occur within the human brain, both at rest and during a motor task involving the stimulated cortical area, as well as in distant regions that are functionally connected (50). Furthermore, the effect might fade away in the sham tDCS rather than in the active tDCS group (51, 52). Therefore, it can be concluded that tDCS effectively alleviates pain perception at the central level, TENS contributes to pain improvement at the peripheral level, and exercises enhance the overall quality of life for patients experiencing cervical radiculopathy.

Limitations

Initially, while the estimated effect size appears promising (d = 1.67), the obtained sample size might be insufficient to extrapolate the findings to a broader population once the study is concluded. Additionally, being a single-center study could impact the generalizability due to potential geographical variations among individuals, and lack of follow-up were some of the limitations of the study. Discrepancies have been observed in the initial characteristics of the experimental and control groups with regard to age. The experimental group seems to comprise individuals who are somewhat younger compared to those in the control group, with an estimated age gap of approximately 2 years. Nevertheless, it's worth noting that previous research has consistently indicated that the most commonly affected age group by CR ranges from 13 to 91 years old, and no study has demonstrated that the effectiveness of the intervention is influenced by minor differences in age.

Strength of the study and Future recommendations

The treatment provided to patients was straightforward to administer. This ease of application is beneficial as it can simplify the implementation of the treatment protocol, making it more accessible and feasible for healthcare providers and patients alike. Furthermore, a significant positive aspect of the treatment approach was the absence of any adverse effects. The fact that none of the patients experienced any harmful reactions to the treatment is a crucial finding as it indicates the safety and tolerability of the interventions used. Utilizing functional MRI and EEG in further research can enhance the evidence base for the treatment approach and provide a more in-depth understanding of its effects on the brain.

Conclusion

The inferences withdrawn from the study stated that when tDCS was given in combination with TENS and exercises, pain and quality of life were effectively improved in patients with cervical radiculopathy by modulating the pain perception at central and peripheral levels.

Author’s contributions

Nidhi Sharma: Concept and design of the study, data analysis, and interpretation of data; Drafting the article or revising it critically for important intellectual content; Final approval of the version to be published.

Sidharth Bansal: Critical revision of the manuscript, analysis, and interpretation of data; Drafting the article.

Orneesh Dube: conducted the research, provided research materials, acquired, and analyzed the data.

Simranjeet Kaur: Drafting the article or revising it critically for important intellectual content, Final approval of the version to be published.

Parveen Kumar: Acquisition of the data, critical revision of the manuscript, final approval of the version to be published; and Aptitude to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Gaurav Kapoor: Drafting the article or revising it critically for important intellectual content, final approval of the version to be published.

All the authors approved the manuscript.

Funding None.

Conflicts of interest Authors have no conflict of interest to declare.