Clinical and Brain Activity Assessment Before and After Physiotherapy in People With Chronic Non-specific Neck Pain

Predictors of Response After Physiotherapy Treatment in People With Chronic Non-specific Neck Pain

The goal of this clinical trial is to investigate whether electroencephalographic features are associated with the multidimensional clinical characteristics of adults with chronic non-specific neck pain and whether clinical and brain function measures change following physiotherapy. Participants with chronic non-specific neck pain will receive six weekly treatment sessions consisting of a manual physiotherapy and neck-specific exercise programme, including a home exercise programme. Clinical, psychophysical, and 64-channel electroencephalographic assessments will be performed at baseline and approximately one week after completion of the intervention. Clinical outcomes will also be reassessed 12 weeks after the last treatment session. Electroencephalographic recordings will be obtained while participants are seated comfortably and instructed to remain relaxed. EEG-derived measures will be examined in relation to pain intensity, neck-related disability, psychological and cognitive-affective factors, sleep quality, and psychophysical pain responses. Healthy participants without chronic neck pain will undergo a comparable baseline assessment to provide reference data for the interpretation of brain function in the clinical group.

Study Overview

• Status: Recruiting
• Conditions: Chronic Neck Pain; Neck Pain Musculoskeletal
• Intervention / Treatment: Other: Manual physiotherapy and neck-specific exercise programme

Detailed Description

This non-randomized interventional study aims to investigate clinical and electroencephalographic characteristics in individuals with chronic non-specific neck pain and to examine changes following a physiotherapy intervention. A healthy control group will also be assessed to provide reference data for comparison with participants with chronic non-specific neck pain.

Participants with chronic non-specific neck pain will undergo a baseline assessment including clinical questionnaires, pain mapping, quantitative sensory testing, and 64-channel electroencephalographic recordings.

Following the baseline assessment, participants with chronic non-specific neck pain will receive six weekly physiotherapy sessions. The intervention will include passive mobilizations of the cervical and thoracic spine, soft tissue mobilizations, and a neck-specific home exercise programme involving neck flexor and extensor training.

The clinical, psychophysical, and electroencephalographic assessments will be repeated approximately one week after completion of the intervention. Perceived recovery, pain intensity, and neck-related disability will also be evaluated approximately 12 weeks after the final treatment session.

The study will examine baseline differences between participants with chronic non-specific neck pain and healthy controls and changes in clinical and electroencephalographic outcomes following physiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Guipuzcoa
    • San Sebastián, Guipuzcoa, Spain, 20012
      • Recruiting
      • Ander Cervantes Benítez
      • Contact: Ander Cervantes Benítez; Phone Number: 5247 34 943 32 66 00; Email: ander.cervantes@deusto.es
      • Sub-Investigator: Ander Cervantes Benítez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Chronic non-specific neck pain (>3 months duration)
• Willing and able to sign informed consent for study participation

Exclusion Criteria:

• Concomitant neurological or psychiatric disease apart from depression (especially severe mental disorder or psychopathology)
• Regular (daily) intake of benzodiazepines
• Signs of severe disease, cervical myelopathy, tumour, rheumatic diseases or a neurological pathology of central origin
• Neck pain of traumatic origin or as a result of whiplash
• Previous surgical intervention of the cervical spine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Physiotherapy group; Participants with chronic non-specific neck pain will receive a 6-week physiotherapy intervention consisting of six individual treatment sessions, including manual therapy directed at the cervical and thoracic regions, together with a home exercise program. Clinical and brain activity assessments will be performed before the intervention and approximately one week after completion of the intervention.	Other: Manual physiotherapy and neck-specific exercise programme; The physiotherapy intervention will consist of six weekly sessions combining manual physiotherapy and a neck-specific exercise programme. Manual physiotherapy will include passive mobilisations of the cervical and thoracic spine and soft tissue techniques. The exercise programme will include daily home exercises targeting cervical mobility and neuromuscular control, including neck flexor and neck extensor training. The intervention is based on the protocol described by Villanueva-Ruiz et al. (2025).; Other Names: Manual therapy and neck exercise
No Intervention: Healthy control group; Healthy participants without chronic neck pain will undergo baseline clinical, psychophysical, and electroencephalographic assessments for comparison with participants with chronic non-specific neck pain. They will not receive the physiotherapy intervention or undergo a post-intervention assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Rating of Change (GROC) scale	It is a single-item patient-reported outcome that aims to quantify a patient's perceived improvement or deterioration over time. The questionnaire is scored with 7 positive items to assess the patient's subjective improvement progressively. It also presents 7 negative items to assess whether the patient has worsened. The 0 is defined as no improvement or worsening.	Post-intervention (approximately 1 week after treatment completion and 12 weeks after the last treatment session)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Pain Rating Scale (NPRS)	11-point tool used to measure pain intensity from 0 (no pain) to 10 (worst pain imaginable)	Baseline and post-intervention (approximately 1 week after treatment completion and 12 weeks after the last treatment session)
Neck Disability Index (NDI)	The Neck Disability Index consists of 10 items assessing disability related to neck pain. Each item is scored from 0 to 5, giving a total score from 0 to 50. Higher scores indicate greater neck-related disability. The score may also be expressed as a percentage from 0% to 100%.	Baseline and post-intervention (approximately 1 week after treatment completion and 12 weeks after the last treatment session)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electroencephalographic spectral characteristics	Spectral characteristics will be derived from 64-channel electroencephalography recorded while participants are seated comfortably with their eyes closed in a quiet environment and instructed to remain relaxed and minimize movement. Mean peak alpha frequency will be reported in hertz (Hz) at baseline and post-intervention.	Baseline and post-intervention (approximately 1 week after treatment completion)
Pain Catastrophizing Scale (PCS)	The Pain Catastrophizing Scale consists of 13 items scored from 0 to 4. The total score ranges from 0 to 52, with higher scores indicating greater pain catastrophizing.	Baseline and post-intervention (approximately 1 week after treatment completion)
Hospital Anxiety and Depression Scale (HADS)	Anxiety and depressive symptoms will be assessed using the 14-item Hospital Anxiety and Depression Scale. The anxiety and depression subscale scores will be summed to obtain a total score ranging from 0 to 42, with higher scores indicating greater psychological distress.	Baseline and post-intervention (approximately 1 week after treatment completion)
Central Sensitization Inventory (CSI)	Symptoms associated with central sensitization will be assessed using Part A of the 25-item Central Sensitization Inventory. The total score ranges from 0 to 100, with higher scores indicating greater symptom severity.	Baseline and post-intervention (approximately 1 week after treatment completion)
Tampa Scale for Kinesiophobia-11	Fear of movement will be assessed using the 11-item Tampa Scale for Kinesiophobia. The total score ranges from 11 to 44, with higher scores indicating greater kinesiophobia.	Baseline and post-intervention (approximately 1 week after treatment completion)
Sleep quality	Sleep quality will be assessed using a single 0-to-10 numerical rating scale, where 0 indicates the worst possible sleep quality and 10 indicates the best possible sleep quality.	Baseline and post-intervention (approximately 1 week after treatment completion)
Pain mapping	Participants will indicate the location and extent of their pain using a digital body chart. Total pain extent will be calculated as the percentage of the body chart area marked as painful.	Baseline and post-intervention (approximately 1 week after treatment completion)
Pressure pain threshold	Pressure pain threshold will be assessed using a pressure algometer with a 1-cm² contact surface. Participants will be instructed to press a button when the sensation first changes from pressure to pain. Measurements will be performed at the most painful cervical location and at the contralateral hand. Three measurements will be obtained at each anatomical location, and the mean of the three measurements will be used for analysis. Values from the cervical location and the hand will be reported separately. Results will be reported in kilopascals.	Baseline and post-intervention (approximately 1 week after treatment completion)
Cold pain threshold	Cold pain threshold will be assessed as part of a quantitative sensory testing protocol using the MSA Thermotest (Somedic) with a 9-cm² contact thermode. The baseline temperature will be set at 32°C, and the minimum safety limit will be 5°C. Temperature will decrease at a rate of 1°C/s. Participants will press a button when the cold sensation first becomes painful, immediately stopping the stimulus. Three valid consecutive measurements will be obtained, and their mean temperature will be used for analysis. Results will be reported in degrees Celsius.	Baseline and post-intervention (approximately 1 week after treatment completion)
Heat pain threshold	Heat pain threshold will be assessed as part of a quantitative sensory testing protocol using the MSA Thermotest (Somedic) with a 9-cm² contact thermode. The baseline temperature will be set at 32°C, and the maximum safety limit will be 50°C. Temperature will increase at a rate of 1°C/s. Participants will press a button when the heat sensation first becomes painful, immediately stopping the stimulus. Three valid consecutive measurements will be obtained, and their mean temperature will be used for analysis. Results will be reported in degrees Celsius.	Baseline and post-intervention (approximately 1 week after treatment completion)
Temporal summation of pain	Mechanical temporal summation of pain will be assessed using calibrated pinprick stimulators (MRC Systems). Participants will rate the perceived pain intensity of a single 256-mN pinprick stimulus and the overall pain intensity elicited by a series of 10 pinprick stimuli of the same force applied at a rate of 1 stimulus per second. Pain intensity will be rated using a numerical rating scale ranging from 0, no pain, to 10, worst imaginable pain. The temporal summation ratio will be calculated by dividing the pain rating for the series of 10 stimuli by the pain rating for the single stimulus. When the pain rating for the single stimulus is 0, a value of 1 will be used as the denominator to avoid division by zero. Higher ratios indicate greater temporal summation of pain.	Baseline and post-intervention (approximately 1 week after treatment completion)
Conditioned pain modulation	Conditioned pain modulation will be assessed using the cold pressor test as the conditioning stimulus and pressure pain threshold as the test stimulus. Participants will immerse the foot contralateral to the most painful cervical location in an insulated container filled with cold water, initially set at 10°C, for up to 2 minutes. The water temperature may be adjusted to achieve a pain intensity of approximately 5 out of 10. Immediately after removal of the conditioning stimulus, pressure pain threshold will be measured three times at the cervical location, with 15 seconds between measurements, and the mean of the three measurements will be used for analysis. The conditioned pain modulation response will be calculated as the absolute change in pressure pain threshold between the pre-conditioning and post-conditioning measurements and reported in kilopascals (kPa). Higher positive values indicate greater endogenous pain inhibition.	Baseline and post-intervention (approximately 1 week after treatment completion)

Collaborators and Investigators

• Sponsor: Ander Cervantes Benítez

Publications and helpful links

General Publications

• Furman AJ, Meeker TJ, Rietschel JC, Yoo S, Muthulingam J, Prokhorenko M, Keaser ML, Goodman RN, Mazaheri A, Seminowicz DA. Cerebral peak alpha frequency predicts individual differences in pain sensitivity. Neuroimage. 2018 Feb 15;167:203-210. doi: 10.1016/j.neuroimage.2017.11.042. Epub 2017 Nov 21.
• Chowdhury NS, Bi C, Furman AJ, Chiang AK, Skippen P, Si E, Millard SK, Margerison SM, Spies D, Keaser ML, Da Silva JT, Chen S, Schabrun SM, Seminowicz DA. A novel cortical biomarker signature predicts individual pain sensitivity. medRxiv [Preprint]. 2024 Nov 5:2024.06.16.24309005. doi: 10.1101/2024.06.16.24309005.
• Bott FS, Zebhauser PT, Hohn VD, Turgut O, May ES, Tiemann L, Gil Avila C, Heitmann H, Nickel MM, Day MA, Adhia DB, Ashar YK, Wager TD, Granovsky Y, Yarnitsky D, Jensen MP, Gross J, Ploner M. Exploring electroencephalographic chronic pain biomarkers: a mega-analysis. EBioMedicine. 2025 Oct;120:105955. doi: 10.1016/j.ebiom.2025.105955. Epub 2025 Sep 30.
• Heitmann H, Gil Avila C, Nickel MM, Ta Dinh S, May ES, Tiemann L, Hohn VD, Tolle TR, Ploner M. Longitudinal resting-state electroencephalography in patients with chronic pain undergoing interdisciplinary multimodal pain therapy. Pain. 2022 Sep 1;163(9):e997-e1005. doi: 10.1097/j.pain.0000000000002565. Epub 2021 Dec 15.
• Zabala Mata J, Lascurain-Aguirrebena I, Dominguez Lopez E, Azkue JJ. Enhanced Pronociceptive and Disrupted Antinociceptive Mechanisms in Nonspecific Chronic Neck Pain. Phys Ther. 2021 Mar 3;101(3):pzaa223. doi: 10.1093/ptj/pzaa223.
• Villanueva-Ruiz I, Falla D, Saez M, Araolaza-Arrieta M, Azkue JJ, Arbillaga-Etxarri A, Lersundi A, Lascurain-Aguirrebena I. Manual therapy and neck-specific exercise are equally effective for treating non-specific neck pain but only when exercise adherence is maximised: A randomised controlled trial. Musculoskelet Sci Pract. 2025 Jun;77:103319. doi: 10.1016/j.msksp.2025.103319. Epub 2025 Mar 21.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 31, 2026
• First Submitted That Met QC Criteria: August 5, 2026
• First Posted (Actual): August 10, 2026

Study Record Updates

• Last Update Posted (Actual): August 10, 2026
• Last Update Submitted That Met QC Criteria: August 5, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Therapeutics; Complementary Therapies; Physical Therapy Modalities; Rehabilitation; Musculoskeletal Manipulations
• Other Study ID Numbers: FST_CCNE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A final decision regarding individual participant data sharing has not yet been made. Pseudonymized individual participant data underlying the results reported in the main publications may be made available through an Open Science Framework repository upon publication. Data sharing will depend on participant consent, approval by the study investigators and relevant ethics bodies, and compliance with applicable data protection and institutional requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No