The present clinical trial is justified, with the primary objective of comparing the effectiveness of EDN combined with therapeutic exercise versus therapeutic exercise alone in patients with CNSNP, evaluating its impact on disability, pain, strength, cervical range of motion, quality of life, and sleep.

This study will be conducted as a randomized, controlled, parallel-group, single-blind clinical trial (assessor-blinded), with two intervention arms: (1) EDN combined with therapeutic exercise and (2) therapeutic exercise alone in patients with CNSNP. Participants will be randomly assigned to 1 of the 2 groups in a 1:1 ratio.

This protocol has been developed in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines (Checklist 1). The study will be conducted at the Clinical Unit of the Faculty of Health Sciences, University of Almería, Spain. A SPIRIT flow diagram and a structured schedule of enrollment, interventions, and assessments have been included to improve methodological transparency and reproducibility.

This study was approved by the Research Ethics Committee of the University of Almería under reference number AP-0429‐2023-C4-F2 and was prospectively registered at ClinicalTrials.gov under identifier NCT06522893. The study will be conducted in accordance with the ethical standards of the Declaration of Helsinki (World Medical Association). All participants will receive verbal and written information about the study and will provide written informed consent before participation. The manuscript does not include an individual's data in any form (including individual images, videos, or identifiable personal details).

A total of 70 patients aged 30 to 68 years with CNSNP of more than 3 months’ duration, who are not currently receiving other treatments, will be recruited. Participants will be recruited from internal and external populations associated with the University of Almería through flyers, emails, and informational posters. Interested individuals will contact a researcher via email or telephone, who will schedule an in-person appointment at the outpatient clinical unit affiliated with the Faculty of Health Sciences.

During this initial visit, a physiotherapist blinded to treatment allocation will assess the eligibility of participants according to the inclusion and exclusion criteria. Following this assessment, patients will be randomly assigned to 1 of 2 groups and will receive the corresponding intervention from 2 trained investigators skilled in the study techniques. All participants will provide written informed consent in accordance with the Declaration of Helsinki (World Health Organization; see Figure 1).

To improve treatment fidelity and intervention standardization, all physiotherapists involved in the study will receive prior training regarding intervention delivery, outcome assessment procedures, and adverse event reporting. Standardized treatment records and session checklists will be used throughout the study.

Participants were not directly involved in the design or conduct of this trial. However, feedback regarding feasibility, acceptability, treatment burden, and participant satisfaction will be collected during follow-up visits to inform future clinical research and implementation strategies.

To ensure participant safety and sample homogeneity, exclusion criteria were operationally defined prior to recruitment. Severe cervical pathology was defined as cervical myelopathy, progressive cervical radiculopathy with neurological deficits, fracture, tumor, inflammatory cervical disease, severe cervical stenosis, or other red-flag conditions requiring medical management. All participants underwent a standardized clinical screening based on current neck pain clinical practice guidelines before enrollment. History of spinal surgery was defined as any previous cervical spine surgical procedure, including decompression, discectomy, fusion, arthroplasty, or stabilization surgery. Coagulation disorders included diagnosed bleeding disorders or conditions requiring special precautions for needling procedures [4,28-30]. Prior to enrollment, all participants will undergo a standardized screening examination performed by a physiotherapist and confirmed by a rehabilitation physician when necessary. Screening will include medical history, neurological examination, assessment of red flags for serious spinal pathology, and review of available imaging reports when clinically indicated (Textbox 1).

Participants were not directly involved in the design or conduct of this trial. Feedback on the feasibility and acceptability of the intervention will be collected during follow-up to inform future research.

Following the initial assessment, 70 patients with CNSNP will be randomly assigned to 1 of 2 groups: the experimental group receiving EDN plus specific therapeutic exercise or the control group receiving specific therapeutic exercise alone. EDN will be delivered by physiotherapists with formal postgraduate training in invasive physiotherapy and at least 3 years of clinical experience in ultrasound-guided EDN procedures.

During the study, participants will receive only the assigned intervention and will not be permitted to combine it with medications or other treatments. Any interference with the assigned treatment will result in study exclusion. Participants may withdraw from the study at any time, and the assigned interventions may be suspended or modified based on the evolution of symptoms (eg, adverse effects). All adverse events will be reported to the principal investigator, who will monitor affected patients and investigate potential causes.

To promote adherence, participants will be provided with a schedule card listing all treatment sessions, and weekly reminders will be sent via phone call, email, or WhatsApp.

At the start of the study, demographic and clinical data will be collected, and all outcome measures will be assessed at 3 time points: baseline (preintervention), immediate posttreatment (1 d after the last session), and short-term follow-up (2 mo postintervention). Outcome assessments will be performed by a blinded evaluator using standardized procedures and calibrated instruments to improve measurement reliability and reproducibility.

The primary outcome is the Neck Disability Index (NDI), a 10-item questionnaire assessing activities of daily living. Each item is scored on a 0‐5 Likert scale. Total scores are converted to percentages (0%‐100%), with 0% indicating full independence and 100% indicating complete dependence [38,39].

Secondary outcome measures include the following:

These outcome measures provide a comprehensive assessment of pain, disability, psychological factors, quality of life, and cervical muscle performance, allowing evaluation of both the immediate and short-term effects of the interventions.

The sample size was calculated for the primary outcome, the NDI, based on detecting a clinically meaningful between-group difference of 7.5 points, which is consistent with previous studies on the responsiveness of the NDI. Assuming a standard deviation of 10.58 points, a 2-sided significance level of .05, and 80% statistical power, the required sample size was 32 participants per group. To account for an anticipated 10% (3/32) loss to follow-up, the final target sample size was increased to 35 participants per group, resulting in a total sample of 70 participants.

Participants will be randomly assigned to either the experimental group (EDN plus therapeutic exercise) or the control group (therapeutic exercise alone) using a computer-generated randomization sequence created by an independent statistician.

Allocation concealment will be ensured using sequentially numbered, opaque, sealed, tamper-evident envelopes prepared by an independent researcher not involved in participant recruitment, outcome assessment, or treatment administration. Envelopes will be opened sequentially only after completion of the baseline assessment and immediately before the first intervention session.

The outcome assessor will remain blinded to group allocation throughout the trial. Participants and treating physiotherapists cannot be blinded due to the nature of the interventions.

Data will be analyzed using SPSS (version 28.0; IBM Corp) and will follow the intention-to-treat principle, whereby all randomized participants will be analyzed in the groups to which they were originally assigned, regardless of treatment adherence or completion. Additionally, a per-protocol analysis will be conducted including participants who complete at least 80% (5/6) of the in-person treatment sessions. All analyses will be conducted by a statistician blinded to group allocation.

Descriptive statistics will be calculated for all variables. Continuous variables will be presented as mean (SD) or median (IQR), depending on the data distribution, while categorical variables will be expressed as frequencies and percentages.

Baseline comparability between groups will be assessed using independent Student t tests for normally distributed continuous variables, Mann-Whitney U tests for nonnormally distributed variables, and chi-square tests for categorical variables. Normality will be evaluated using the Kolmogorov-Smirnov test and visual inspection of histograms.

A statistically significant group × time interaction will be interpreted as evidence of differential treatment effects over time. To evaluate the effects of the intervention over time and between groups, linear mixed-effects models will be used, including group (experimental vs control), time (baseline, postintervention, and 2-mo follow-up), and the group × time interaction as fixed effects, with participants included as random effects. This approach allows appropriate handling of repeated measures and missing data.

If model assumptions are not met, appropriate nonparametric alternatives (eg, Friedman test for within-group comparisons and Mann-Whitney U test for between-group comparisons with adjusted post hoc analyses) will be applied. Adjustment for multiple comparisons among secondary outcomes will be performed using the Holm-Bonferroni procedure.

Missing data will be handled using multiple imputation methods under the assumption of missing at random. Sensitivity analyses will be conducted to assess the robustness of the findings. Dropouts and losses to follow-up will be reported and compared between groups. Twenty imputed datasets will be generated using multiple imputation procedures.

The primary end point will be the between-group difference in change in NDI scores from baseline to postintervention. Postintervention was defined as 1 day after completion of the sixth treatment session. Age, sex, and baseline NDI values will be explored as potential covariates if baseline imbalance is detected. Secondary outcomes will include changes in Visual Analog Scale, McGill Pain Questionnaire, quality of life SF-36, Tampa Scale of Kinesiophobia, cervical range of motion, Pittsburgh Sleep Quality Index, PCS, pressure pain threshold, cervical isometric strength, and cervical flexor endurance. Effect sizes (eg, Cohen d) will be calculated to assess the magnitude of differences.

Additionally, the clinical relevance of the findings will be assessed by comparing observed changes with established minimal clinically important differences. Based on previous studies in patients with neck pain, a change of approximately 7.5 points on the NDI and 1.5 points on pain intensity scales has been considered clinically meaningful and will be used to aid the interpretation of clinical relevance [49]. For other secondary outcomes, where established minimal clinically important differences are available, these will be considered to aid the interpretation of clinical significance.

The study is single-blind; both the outcome assessor and the statistician performing data analysis will remain blinded to group allocation. Participants will be instructed not to disclose details of their intervention to the assessor. The success of blinding will be evaluated at the end of the trial by asking the assessor to guess each participant’s group assignment, and the results will be reported.

All participant data will be recorded on paper case report forms and stored in locked cabinets in the University of Almería outpatient clinic. Digital data will be entered into a password-protected SPSS software database.

Data entry will be double-checked for accuracy by the data manager. Backups of digital data will be maintained on a secure university server. Only authorized personnel (principal investigator, statistician, and outcome assessor) will have access to identifiable participant data.

Data will be retained for a minimum of 10 years following completion of the study, in accordance with university and national regulations.

An adverse event is defined as any undesirable and unintended sign, symptom, or medical condition occurring in a participant following receipt of a study intervention, regardless of whether a causal relationship with the administered treatment exists.

To date, no significant risks have been reported for any of the interventions; however, minor adverse effects—such as a temporary increase in pain or the development of bruising—may occur, which can be minimized through the physiotherapist’s anatomical knowledge and clinical experience.

All adverse events will be carefully monitored and recorded throughout the study. The physiotherapists responsible for the intervention will document the nature, intensity, duration, and potential causes of each adverse event, as well as any corrective actions taken.

If a significant adverse event is identified, the need to temporarily or permanently suspend the intervention for the affected participant will be assessed immediately, following predefined safety criteria. The ethics committee and the principal investigator will be notified of any serious adverse events in accordance with applicable regulatory guidelines.

Participants will also receive continuous information on the prevention and management of possible minor side effects and will be encouraged to report any new or unexpected symptoms immediately. These measures are intended to ensure participant safety and maintain the integrity of the study.

No formal interim analysis is planned due to the short duration and minimal risk of the interventions. However, the study may be suspended for any participant in the event of serious adverse events, as determined by the principal investigator in consultation with the Research Ethics Committee.

All patients and physiotherapists will receive specific information about the study in writing and will have a chance to discuss the procedures with a member of the study team before providing consent to participate. They will also be informed that they can withdraw from the study at any time. Participants who agree to participate in the study will sign 2 copies of the informed consent form, one that will be kept in the trial records and one for the participant.

The data collected from each patient will be stored in a closed locker in an office at the University of Almería, and only the physiotherapists evaluators will have access to that information. Subsequently, the data will be entered and saved by the statistician on a password-protected laptop to maintain confidentiality. Eligibility criteria, results, and analyses will not be modified after registration of the first participant.

The recruitment of patients started on November 1, 2025, and was completed by December 31, 2025. All follow-up data are expected to be collected by March 31, 2026. Data analysis, manuscript preparation, and submission to peer-reviewed scientific journals will be carried out during 2026 (Table 2).

Due to the increasing prevalence of musculoskeletal diseases, such as cervicalgia, and their socioeconomic impact globally [8-10], the importance of finding increasingly cost-effective and evidence-based treatment options for the approach increases. CNSNP is frequently associated with musculoskeletal disorders, including decreased strength and endurance of the deep cervical muscles, range of motion restrictions, postural disturbances, and peripheral and central sensitization [50,51].

EDN and therapeutic exercise are minimally invasive techniques used in the treatment of musculoskeletal pain, including chronic neck pain. EDN combines dry needling with electrical stimulation, seeking to enhance its analgesic and muscle relaxation effects [23,24]. Specific therapeutic exercise targeting the cervical region has been shown to be one of the most effective interventions for reducing pain intensity and functional disability in this population [13,15]. This type of exercise seeks to improve activation and motor control of the deep cervical muscles, restore the support and stabilization function of the cervical spine, and increase muscle strength and endurance, which contribute to improved load-bearing capacity and pain reduction. Furthermore, exercise promotes joint mobility, local circulation, and central nervous system modulation, generating both peripheral and central effects on pain perception [18,19,52].

Although both techniques are used in clinical practice and there are studies supporting their use, there is still no conclusive evidence directly comparing their efficacy and safety in patients with CNSNP. Comparing these 2 interventions with isolated therapeutic exercise can provide valuable information to determine which offers better results in terms of pain reduction, functional improvement, quality of life, and safety.

Therefore, this clinical trial emerges as a necessity to fill this gap in the evidence base, enabling more informed and evidence-based decision-making by health care professionals caring for patients with CNSNP. Furthermore, the results could contribute to optimizing treatment protocols and improving clinical outcomes in this population.

One of the main advantages of this protocol is that it is not intended to replace traditional rehabilitation but rather to provide complementary and/or parallel treatments in order to achieve more effective outcomes over time.

The main difficulties and limitations of the protocol include maintaining participant adherence throughout the course of the study, the impossibility of blinding both participants and physiotherapists—which could introduce bias—and the inability to control external aggravating factors of the pathology, such as high workload, elevated stress levels, among others. In addition, a sham EDN or attention-control intervention was not included in the study design. Therefore, nonspecific effects related to therapist contact time, patient expectations, or contextual factors cannot be completely excluded when interpreting the study findings. Consequently, the study will evaluate the effectiveness of adding EDN to usual exercise-based care rather than isolating the specific physiological effects of EDN itself. Accordingly, any observed between-group differences should be interpreted with caution, as they may reflect both specific intervention effects and nonspecific contextual influences.

Nevertheless, to facilitate adherence and minimize dropouts during the study, participants will receive reminders by phone call or WhatsApp regarding the date and time of each session. In addition, patients will be periodically informed of their improvements and progress, with the aim of motivating them to remain engaged in the treatment.