Pain Phenotypes in Individuals With Multiple Sclerosis

Pain Phenotyping in Multiple Sclerosis Based on IASP Criteria

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Sclerosis; Chronic Pain
• Intervention / Treatment: Diagnostic test: Pain classification method

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Nisa TURUTGEN, Msc.; Phone Number: 1499 00902742651300; Email: nisa.turutgen@ksbu.edu.tr

Study Locations

• Turkey (Türkiye)
  • Turkiye
    • Kütahya, Turkiye, Turkey (Türkiye), 43100
      • Kutahya Health Sciences University Physical Medicine and Rehabilitation Department
      • Contact: Ismail SARACOGLU, Head of Department; Phone Number: 1499 002742651300; Email: ismail.saracoglu@ksbu.edu.tr
      • Principal Investigator: Nisa TURUTGEN, Msc.
      • Principal Investigator: Dursun CEYLAN, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Participants meeting the inclusion criteria will be taken for this cross-sectional study. Individuals with MS who apply to Kutahya Health Sciences University Hospital Physiotherapy Department will be screened for eligibility by their clinic physicians and will then be asked to participate in this study.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative sensory test: static tactile mechanical threshold	Von Frey Monofilaments (2 gr- 26 gr) will be used assessment for the static tactile mechanical detection threshold.	10 minutes
Quantitative sensory test: hot-cold pain threshold	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.	5 minutes
Quantitative sensory test: static mechanical allodynia	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.	5 minutes
Quantitative sensory test: dynamic mechanical allodynia	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 minutes
Quantitative sensory test: vibration sense	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.	5 minutes
Margolis Pain Diagram	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.	1 minute

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Pain Rating Scale	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.	1 minute
Pain Catastrophizing Scale (PCS)	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.	5 minutes
Modified Fatigue Impact Scale (MFIS)	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.	1 minute
Health-Related Quality of Life	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 minutes
Multiple Sclerosis Disease Severity	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.	5 minutes
Overactive Bladder Questionnaire-V8 (OAB-V8)	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.	5 minutes
Hospital Anxiety and Depression Scale (HADS)	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.	5 minutes
Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)	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.	10 minutes

Collaborators and Investigators

• Sponsor: Kutahya Health Sciences University

Study record dates

Study Major Dates

• Study Start (Estimated): August 15, 2026
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): September 15, 2027

Study Registration Dates

• First Submitted: August 11, 2026
• First Submitted That Met QC Criteria: August 11, 2026
• First Posted (Actual): August 14, 2026

Study Record Updates

• Last Update Posted (Actual): August 18, 2026
• Last Update Submitted That Met QC Criteria: August 14, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: CHRONIC PAIN; NEUROPATHIC PAIN; MULTIPLE SCLEROSIS; NOCIPLASTIC PAIN
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Nervous System Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Multiple Sclerosis; Chronic Pain; Neuralgia; Nociplastic Pain
• Other Study ID Numbers: NisaPHD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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