EFFECT OF TRANSCUTANEOUS ELECTRONEURO-STIMULATION OF THE VAGUS NERVE ON JOINT PAIN SEQUELAE OF CHIKUNGUNYA FEVER IN THE LOWER LIMBS

This study aims to evaluate the efficacy of transcutaneous electrical nerve stimulation (taVNS) in reducing chronic lower limb joint pain in individuals with sequelae of Chikungunya fever. Post-Chikungunya chronic pain is a prevalent and disabling condition associated with persistent inflammation, neuroimmune alterations, and central sensitization mechanisms, which negatively impact functionality and quality of life. Given the lack of specific treatments with established efficacy, vagal neuromodulation emerges as a promising approach. This is a randomized, controlled, parallel, three-arm clinical trial involving adults with chronic joint pain lasting at least three months after Chikungunya infection. Participants will be randomly assigned (1:1:1) to one of three groups: taVNS, peripheral TENS (active control), or sham stimulation (placebo). The study will use a double-blind design for both participants and evaluators. The interventions will take place twice a week for three weeks, totaling six 30-minute sessions. taVNS will be applied to the superior concha of the left ear using standardized parameters, with intensity adjusted to a comfortable sensory threshold. The active control group will receive TENS on the painful joint, while the sham group will receive auricular stimulation without effective vagal activation. The primary outcome will be the change in pain intensity, assessed using the Visual Analogue Scale. Secondary outcomes will include quality of life (SF-36), pressure pain threshold, joint temperature, and functional performance (Timed Up and Go). The analysis will follow the linear mixed-effects using repeated measures models. The results are expected to strengthen the evidence for taVNS as a non-pharmacological intervention for managing chronic post-Chikungunya pain.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain and Comorbid Emotional Problems; Chronic Pain Management
• Intervention / Treatment: Device: Transcutaneous vagus nerve electrical stimulation; Device: Transcutaneous eletrical nerve stimuation; Device: Transcutaneous electrical nerve stimulation

• Study Type: Interventional
• Enrollment (Estimated): 51
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50670-420
      • Federal University of Pernambuco - Department of Physiotherapy, Electrophototherapy Laboratory

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• People of either sex who are over 18 years of age, Clinical diagnosis of Chikungunya confirmed by laboratory test and/or medical report; Chronic joint pain in one or more lower limb joints lasting at least 3 months after infection; Ability to ambulate independently or with assistive devices; Intact skin integrity in the auricular region and areas of electrode placement; Residing in the state of Pernambuco.

Exclusion Criteria:

• Neurological disorders; Decompensated cardiorespiratory diseases; Pre-existing systemic rheumatic diseases prior to Chikungunya infection; History of seizures or epilepsy; Presence of implanted electronic devices (e.g., pacemakers); Pregnancy; Orofacial or ear pain; Skin lesions, infections, or impaired sensation at stimulation sites; Thrombophlebitis, ischemic or ulcerated areas; Neoplasms; Use of medications or substances that increase seizure risk; Current participation in other physiotherapy treatments during the study period; Conditions that prevent attendance at the study site.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Individuals receiving a TENS current application protocol in the superior concha of the left ear, the outer ear area innervated by the auricular branch of the vagus nerve. They recive the tVNS intervention.	Device: Transcutaneous vagus nerve electrical stimulation; The transcutaneous vagus nerve electrical stimulations is a non-pharmacological analgesic intervention for the treatment of pain and has been shown to be beneficial in epilepsy, depression, chronic pain and inflammatory diseases.; Other Names: taVNS
Active Comparator: Group 2; Individuals receiving a TENS current application protocol in a painful lower limb joint (knee or ankle)	Device: Transcutaneous eletrical nerve stimuation; The transcutaneous eletrical nerve stimulation is another non-pharmacological analgesic intervention for the treatment of chronic and acute pain, it has studies about it effectiveness in this types of pain for 50 years.; Other Names: Peripheral TENS
Sham Comparator: G3; individuals receiving a TENS current in the left ear lobe only, an area not innervated by the auricular branch of the vagus nerve, without effective vagal activation	Device: Transcutaneous electrical nerve stimulation; The sham stimulation mimics the sensory experience of active stimulation without producing therapeutic neuromodulatory effects.; Other Names: Sham taVNS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale	The visual analog pain scale (VAS) is used, a one-dimensional instrument for assessing pain intensity. It is a line whose ends are numbered 0-10. One end of the line is marked "no pain" and the other "worst pain imaginable".	Baseline and immediately after the 3-week intervention period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life (SF-36)	The 36-item Medical Outcomes Study Short-Form Health Survey (SF-36) is used to assess quality of life. It consists of 36 items covering 8 domains: Functioning (10 items), physical aspects (4 items), pain (2 items), general health (5 items), vitality (4 items), social aspects (2 items), emotional aspects (3 items), mental health (5 items).	Baseline and post-intervention (3 weeks)
Pressure Pain Threshold	A KRATOS pressure algometer (PA), model DDK electronic, with a flat, circular metal probe with a diameter of 01 cm and a pressure in kilogram force (kgf) is used to measure the pressure pain threshold.	Baseline and post-intervention (3 weeks)
Digital thermography	Joint temperature will be assessed using infrared thermography under controlled environmental conditions to evaluate changes associated with inflammation.	Baseline and post-intervention (3 weeks)
Timed Up and Go	An Android smartphone with the MOMENTUM SCIENCE app installed is used to assess the dynamic balance. The smartphone is attached to the lumbar region between L3 and L5 with a Velcro strap to hold it in place and the Time UP and Go (TUG) test is performed.	Baseline and post-intervention (3 weeks)

Collaborators and Investigators

• Sponsor: Universidade Federal de Pernambuco

Publications and helpful links

General Publications

• Aguiar-Santos M, et al. Spatial analysis of the incidence of Chikungunya fever and associated socioeconomic, demographic and vector infestation factors in municipalities of Pernambuco, Brazil, 2015-2021. 2023;26. Badran BW, et al. Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: a concurrent taVNS/fMRI study and review. Brain Stimul. 2018;11(3):492-500. Botha C, et al. Modulation of parasympathetic nervous system tone influences oesophageal pain hypersensitivity. Gut. 2015;64(4):611-617. Brazil Ministry of Health. Health Surveillance Guide. 5th ed. Brasília (DF): Ministry of Health; 2022. Butt MF, et al. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020;236(4):588-611. Irigoyen MC, et al. Revisiting sympathetic nervous system physiology: what's new? Rev Bras Hipertens. 2014;24(2):9-15. Crossman AR, Neary D. Neuroanatomy: An Illustrated Colour Text. Rio de Janeiro: Elsevier; 1997. Farmer AD, Aziz Q. Vagally mediated analgesia: breath-holding during exhalation as a simple manipulation to reduce pain perception. Pain Med. 2015;16(12):2417-2418. Hamer HM, Bauer S. Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Epilepsy Behav. 2019;83-84. Hartley S, et al. Noninvasive vagus nerve stimulation: a new therapeutic approach for pharmacoresistant restless legs syndrome. Sleep Med. 2023;26(3):629-637. Lopes N, Nozawa C, Linhares REC. General characteristics and epidemiology of emerging arboviruses in Brazil. Rev Pan-Amaz Saude. 2014;5(3). Martinez JE, Grassi DC, Marques LG. Analysis of the applicability of three pain assessment instruments in different care units: outpatient, ward and emergency. Rev Bras Reumatol. 2011;51(4):299-308. Mesquita R, et al. Brazilian-Portuguese version of the SF-36: a reliable and valid quality of life out

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2025
• Primary Completion (Estimated): April 10, 2026
• Study Completion (Estimated): June 15, 2026

Study Registration Dates

• First Submitted: April 4, 2026
• First Submitted That Met QC Criteria: April 4, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Chronic Pain; Therapeutics; Physical Therapy Modalities; Rehabilitation; Anesthesia and Analgesia; Electric Stimulation Therapy; Analgesia; Transcutaneous Electric Nerve Stimulation
• Other Study ID Numbers: 83524324.0.0000.5208

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No