Clinical trial NCT06905171: Habituation of Brain Responses to Sensory Stimuli in Fibromyalgia
Official title: Analysis of Brain Responses and Habituation to Multimodal Sensory Stimuli in Patients with Fibromyalgia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Fibromyalgia
Keywords: Event-Related Potentials
Electroencephalography
Habituation
Lead sponsor: National Council of Scientific and Technical Research, Argentina
Sponsor class: OTHER_GOV
First posted: 2025-04-01
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The cohorts of patients and healthy controls wil be selected from the city of Paraná and surrounding areas. Through the ONG "Fibromialgia Entre Ríos Asociación Civil", the patients will be reached out and asked wether or not they are willing to participate. Additionally, flyer will be hung in major health facilities in the city and made public on social media. The cohort of healthy volunteers will be recruited after the patients for age, genre and socieconomic matching

Brief summary: The goal of this observational study is to assess event-related potentials and habituation in patients with fibromyalgia. The main research questions are:

* Is there a measurable difference in sensory responses between fibromyalgia patients and healthy control?
* Could these measures provide evidence supporting claims of hypersensitivity?

Participants will:

- receive randomized sensory stimuli (auditory, visual, somatosensory, audiovisual, auditory-somatosensory, visual-somatosensory, and auditory-visual-somatosensory) in blocks of 20 trials.

Detailed description: Fibromyalgia is a disorder characterized primarily by widespread musculoskeletal pain. It is often accompanied by symptoms such as fatigue, insomnia, cognitive difficulties, etc. In addition to chronic pain, patients frequently report hypersensitivity to sensory stimuli, both nociceptive and non-nociceptive. Studies using psychophysical and electrophysiological tests have found altered sensory processing in fibromyalgia patients (Lim et al., 2016; McDermid et al., 1996; Staud et al., 2021).

Research focused on event-related potentials (ERPs) have found differences in amplitude in the responses to auditory, nociceptive, and non-nociceptive somatosensory stimuli in fibromyalgia patients (Alanoğlu et al., 2005; De Tommaso et al., 2011; Lorenz, 1998; Montoya et al., 2006). One key aspect evaluated through ERPs is habituation, defined as a decrease in response due to repeated stimulation (Thompson \& Spencer, 1966). In healthy individuals, ERPs amplitude decreases with repeated sensory input due to progressive neuronal response reduction. In fibromyalgia patients, reduced habituation has been observed for laser-induced ERPs (De Tommaso et al., 2011) and somatosensory ERPs (Montoya et al., 2006), though no differences were found for auditory ERPs.

ERPs not only provide information about sensory modalities but also contain non-specific components related to stimulus expectation, motor preparation, and attentional orientation (Gondan \& Röder, 2006). Previous studies have attempted to isolate this non-specific component, as part of habituation may stem from a decrease in its amplitude rather than from a direct sensory response reduction (Young et al., 2022). Using an analytical model, researchers successfully separated this component in experiments with individually or simultaneously presented stimuli, yielding promising results.

In the present study, participants (both fibromyalgia patients and healthy controls) will attend one experimental session in which stimulation in different sensory modalities will take place along with electroencephalographic (EEG) recordings. For each stimulus type, 2 blocks of 20 trials will be performed.The order of the stimulus will be selected randomly, but they can be divided into three categories:

* Unimodal stimulus

  * Auditory (A): a 1000 Hz tone delivered at a comfortable volume through a speaker
  * Visual (V): a checkerboard pattern, inverted every 25 ms, presented on a computer screen.
  * Somatosensory (S): a train of 3 electrical stimuli that elicits a pricking sensation.
* Bimodal stimulus

  * Auditory-Visual (AV)
  * Auditivo-Somatosensory (AS)
  * Visual-Somatosensory (VS)
* Trimodal Stimulus

  * Auditory-Visual-Somatosensory (AVS) The aim of the study is to evaluate neurophysiological parameters related to habituation in multimodal sensory stimulation environments to characterize ERPs in fibromyalgia patients.

Eligibility criteria: Inclusion Criteria:

Fibromyalgia patients:

* Primary diagnosis of fibromyalgia according to the criteria used by the healthcare professional in charge of the patient.
* Other comorbidities are accepted as long as the pain caused by them is less severe than the pain caused by fibromyalgia.
* Willingness and ability to fully understand the content and scope of the experiment and to comply with the experiment instructions.
* Normal or corrected-to-normal vision.
* Normal hearing

Healthy controls:

* No history of neurological diseases, chronic pain or musculoskeletal disorders.
* Willingness and ability to fully understand the content and scope of the experiment and to comply with the experiment instructions.
* Normal or corrected-to-normal vision.
* Normal hearing

Exclusion Criteria:

Fibromyalgia patients:

* Pregnancy
* History of addictive behavior, defined as alcohol, cannabis, opioids or other drugs abuse.
* Presence of fever, tuberculosis, malignant tumors, infectious processes, acute inflammatory processes.
* Lack of cooperation

Healthy controls:

* Pregnancy
* History of chronic pain or musculoskeletal or articular disorders
* History of addictive behavior, defined as alcohol, cannabis, opioids or other drugs abuse.
* Presence of fever, tuberculosis, malignant tumors, infectious processes, acute inflammatory processes.
* Lack of cooperation

Primary outcomes:
measure: Percentual Habituation
timeFrame: Immediately after the intervention
Secondary outcomes:
measure: Fibromyalgia Impact Questionnaire-Revised version (FIQR)
timeFrame: 10 minutes before the intervention
measure: Symptoms Impact Questionnaire (SIQ)
timeFrame: 10 minutes before the intervention
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: 10 minutes before the intervention
measure: VAS Pain
timeFrame: 10 minutes before the intervention
measure: Stimulus saliency
timeFrame: Immediately after the intervention
measure: Event-related potentials amplitude
timeFrame: Immediately after the intervention
measure: Event-related potentials latency
timeFrame: Immediately after the intervention
measure: Non-specific components amplitude
timeFrame: Immediately after the intervention
measure: Non-specific components latency
timeFrame: Immediately after the intervention
Other outcomes:
Locations:
city: Oro Verde
country: Argentina
facility: Faculty of Engineering-National University of Entre Ríos
state: Entre Ríos
Study officials:
affiliation: National Council of Scientific and Technical Research, Argentina (CONICET)
name: Biurrun Manresa
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gondan M, Roder B. A new method for detecting interactions between the senses in event-related potentials. Brain Res. 2006 Feb 16;1073-1074:389-97. doi: 10.1016/j.brainres.2005.12.050. Epub 2006 Jan 20.
citation: Thompson RF, Spencer WA. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev. 1966 Jan;73(1):16-43. doi: 10.1037/h0022681. No abstract available.
citation: Montoya P, Sitges C, Garcia-Herrera M, Rodriguez-Cotes A, Izquierdo R, Truyols M, Collado D. Reduced brain habituation to somatosensory stimulation in patients with fibromyalgia. Arthritis Rheum. 2006 Jun;54(6):1995-2003. doi: 10.1002/art.21910.
citation: Lorenz J. Hyperalgesia or hypervigilance? An evoked potential approach to the study of fibromyalgia syndrome. Z Rheumatol. 1998;57 Suppl 2:19-22. doi: 10.1007/s003930050228.
citation: de Tommaso M, Federici A, Santostasi R, Calabrese R, Vecchio E, Lapadula G, Iannone F, Lamberti P, Livrea P. Laser-evoked potentials habituation in fibromyalgia. J Pain. 2011 Jan;12(1):116-24. doi: 10.1016/j.jpain.2010.06.004. Epub 2010 Aug 4.
citation: Alanoglu E, Ulas UH, Ozdag F, Odabasi Z, Cakci A, Vural O. Auditory event-related brain potentials in fibromyalgia syndrome. Rheumatol Int. 2005 Jun;25(5):345-9. doi: 10.1007/s00296-004-0443-3. Epub 2004 Feb 21.
citation: McDermid AJ, Rollman GB, McCain GA. Generalized hypervigilance in fibromyalgia: evidence of perceptual amplification. Pain. 1996 Aug;66(2-3):133-44. doi: 10.1016/0304-3959(96)03059-x.
citation: Young EL, Mista CA, Jure FA, Andersen OK, Biurrun Manresa JA. An analytical method to separate modality-specific and nonspecific sensory components of event-related potentials. Eur J Neurosci. 2022 Oct;56(7):5090-5105. doi: 10.1111/ejn.15798. Epub 2022 Aug 31.
citation: Staud R, Godfrey MM, Robinson ME. Fibromyalgia Patients Are Not Only Hypersensitive to Painful Stimuli But Also to Acoustic Stimuli. J Pain. 2021 Aug;22(8):914-925. doi: 10.1016/j.jpain.2021.02.009. Epub 2021 Feb 23.
citation: Lim M, Roosink M, Kim JS, Kim HW, Lee EB, Son KM, Kim HA, Chung CK. Augmented Pain Processing in Primary and Secondary Somatosensory Cortex in Fibromyalgia: A Magnetoencephalography Study Using Intra-Epidermal Electrical Stimulation. PLoS One. 2016 Mar 18;11(3):e0151776. doi: 10.1371/journal.pone.0151776. eCollection 2016.