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NCT Number: NCT07766213

Pain Phenotypes in Individuals With Multiple Sclerosis

This observational cross-sectional study aims to determine chronic pain phenotypes in individuals with multiple sclerosis (MS) and to investigate the clinical characteristics associated with different pain phenotypes. Participants with MS and chronic pain will undergo a comprehensive clinical assessment to identify nociceptive, neuropathic, nociplastic, and mixed pain phenotypes. The assessment will include clinical history, pain characteristics and distribution, quantitative sensory testing, pain intensity, disease severity, fatigue, health-related quality of life, and pain catastrophizing. The clinical characteristics of participants with different pain phenotypes will subsequently be compared.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Kutahya Health Sciences University Physical Medicine and Rehabilitation Department

Kütahya, Turkiye, 43100, Turkey (Türkiye)

Location contact

Dursun CEYLAN, MD

PRINCIPAL_INVESTIGATOR

Ismail SARACOGLU, Head of Department

CONTACT

[email protected]

002742651300 ext. 1499

Nisa TURUTGEN, Msc.

PRINCIPAL_INVESTIGATOR

About this study

Multiple sclerosis (MS) is a chronic, progressive, autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal damage. Pain is common among individuals with MS and may substantially affect functioning and quality of life. Different pain mechanisms may coexist in individuals with MS; however, the contribution of nociceptive, neuropathic, nociplastic, and mixed pain phenotypes in this population remains insufficiently characterized.

This cross-sectional observational study will include individuals with a definite diagnosis of MS who experience chronic pain. Participants will undergo a comprehensive clinical assessment to determine their predominant pain phenotype. Pain phenotyping will incorporate clinical history, pain characteristics and distribution, hypersensitivity findings, comorbidities, and quantitative sensory testing.

Quantitative sensory testing will include static tactile mechanical detection, thermal perception, static mechanical allodynia, dynamic mechanical allodynia, and vibration perception. Testing will be performed under standardized environmental conditions and initially at the participant's most painful body region.

In addition to pain phenotyping, pain intensity, pain distribution, pain catastrophizing, fatigue, health-related quality of life, and MS disease severity will be evaluated. Clinical characteristics will subsequently be compared among participants with different pain phenotypes to investigate the potential clinical impact of pain mechanisms in individuals with MS.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 years or older
  • Definite diagnosis of multiple sclerosis according to the McDonald criteria
  • No MS relapse or high-dose steroid treatment within the previous 3 months
  • Pain intensity ≥2 on the Numeric Rating Scale in at least one body region for at least 3 months
  • Ability to read, understand, and communicate in Turkish

Exclusion criteria

  • Pregnancy
  • Severe psychiatric disorder and/or severe cognitive impairment confirmed by a neurologist or neuropsychiatrist
  • Presence of a serious pathology or disease that may compromise the assessment process or affect clinical decision-making, including metastasis, cancer, untreated or unhealed fractures, neurological disorders other than multiple sclerosis, or a history of diabetes

Treatment and study plan

Pain classification method

Diagnostic Test

A current clinical algorithm will be used to determine the predominant type of pain in individuals with MS. The classification to diagnose nociceptive, neuropathic and nociplastic pain will based on a recent method developed by Nijs et al. This method consists of seven steps in total. These steps question the following, respectively: duration of pain, pain distribution, presence of nociceptive pain, presence of neuropathic pain, phenomenon of hypersensitivity, presence of hypersensitization and presence of specific comorbidity. Besides, inter-rater and intra-rater reliability of pain classification algorithm will be determined by two independent researchers.

Primary outcomes

  1. Quantitative sensory test: static tactile mechanical threshold

    Time frame: 10 minutes

    Von Frey Monofilaments (2 gr- 26 gr) will be used assessment for the static tactile mechanical detection threshold.

  2. Quantitative sensory test: hot-cold pain threshold

    Time frame: 5 minutes

    Coins will be used for the hot-cold pain threshold. The cold sensing test will be done with a coin held at room temperature. The hot sensing test will be done in the form of a coin placed in the pocket and applied to the participant after waiting for 30 minutes.

  3. Quantitative sensory test: static mechanical allodynia

    Time frame: 5 minutes

    A digital algometer device (JTech) will be used for static mechanical allodynia (pressure pain threshold). In the device, the pain sensation will be tested by applying 4 kg of pressure to the participant.

  4. Quantitative sensory test: dynamic mechanical allodynia

    Time frame: 5 minutes

    A soft brush will be used for dynamic mechanical allodynia. The brush will be gently moved over the skin at a speed of 3-5 cm per second in a fixed direction over the patients primary painful area.

  5. Quantitative sensory test: vibration sense

    Time frame: 5 minutes

    128 Hz tuning fork will be used in vibration assessment. The device will be applied over the bony prominences in the painful area of the patient.

  6. Margolis Pain Diagram

    Time frame: 1 minute

    The Margolis Pain Diagram, consists of a dorsal and a ventral drawing body, is used to assess the location and distribution of the pain [20]. Participants will ask to point out the place where they experience pain during the preceding 4 weeks for at least 24 hours.

Secondary outcomes

  1. Numeric Pain Rating Scale

    Time frame: 1 minute

    Pain intensity will be assessed using the 11-point Numeric Rating Scale (NRS). Participants will rate their pain intensity from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain intensity.

  2. Pain Catastrophizing Scale (PCS)

    Time frame: 5 minutes

    Pain catastrophizing will be assessed using the 13-item Pain Catastrophizing Scale (PCS). The scale evaluates three dimensions of pain catastrophizing: rumination, helplessness, and magnification. Each item is scored from 0 to 4, resulting in a total score ranging from 0 to 52. Higher scores indicate greater pain catastrophizing.

  3. Modified Fatigue Impact Scale (MFIS)

    Time frame: 1 minute

    Fatigue will be assessed using the Modified Fatigue Impact Scale (MFIS). The MFIS evaluates the perceived impact of fatigue on physical, cognitive, and psychosocial functioning. It consists of 21 items scored on a 5-point Likert scale from 0 to 4, resulting in a total score ranging from 0 to 84. Higher scores indicate a greater impact of fatigue on daily functioning. Physical, cognitive, and psychosocial subscale scores may also be calculated separately.

  4. Health-Related Quality of Life

    Time frame: 5 minutes

    Health-related quality of life will be assessed using the Short Form-12 Health Survey (SF-12). The questionnaire consists of 12 items and provides physical and mental component scores. Higher scores indicate better health-related quality of life.

  5. Multiple Sclerosis Disease Severity

    Time frame: 5 minutes

    Multiple sclerosis-related neurological disability and disease severity will be assessed using the Expanded Disability Status Scale (EDSS). The EDSS evaluates neurological impairment and disability associated with MS, with higher scores indicating greater neurological disability.

  6. Overactive Bladder Questionnaire-V8 (OAB-V8)

    Time frame: 5 minutes

    Overactive bladder symptoms will be assessed using the Overactive Bladder Questionnaire-V8 (OAB-V8). The questionnaire consists of 8 items evaluating the degree of bother associated with symptoms such as urinary urgency, frequency, nocturia, and urge urinary incontinence. Higher total scores indicate greater symptom burden related to overactive bladder.

  7. Hospital Anxiety and Depression Scale (HADS)

    Time frame: 5 minutes

    Anxiety and depressive symptoms will be assessed using the Hospital Anxiety and Depression Scale (HADS). The scale consists of 14 items divided into two 7-item subscales: the Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and the Hospital Anxiety and Depression Scale-Depression (HADS-D). Each item is scored from 0 to 3, resulting in subscale scores ranging from 0 to 21. Higher scores indicate greater anxiety or depressive symptom severity.

  8. Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

    Time frame: 10 minutes

    Cognitive function will be assessed using the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), a standardized cognitive assessment battery developed for individuals with multiple sclerosis. The battery includes the Symbol Digit Modalities Test (SDMT) for information processing speed, the California Verbal Learning Test-Second Edition (CVLT-II) for verbal learning and memory, and the Brief Visuospatial Memory Test-Revised (BVMT-R) for visuospatial learning and memory. Test scores will be recorded separately, with higher scores generally indicating better cognitive performance.

Study contacts

Contact information is provided by the study sponsor or research team.

Nisa TURUTGEN, Msc.

CONTACT

[email protected]

00902742651300 ext. 1499

Sponsors and collaborators

Lead sponsor

Kutahya Health Sciences University

Other

Registry information

Official study title

Pain Phenotyping in Multiple Sclerosis Based on IASP Criteria

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 14, 2026
Registry last updated
Aug 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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