Central Sensitization in Painful and Painless Diabetic Peripheral Neuropathy

NCT07316322 | Not Yet Recruiting

• 1 other identifier: 1003
• Study Type: observational
• Target: 128
• Locations: 1 country
• Sites: 1

Brief Summary

This research is structured as a cross-sectional observational study. The primary objective is to compare central sensitization across painful and painless phenotypes of diabetic peripheral neuropathy. The study will be conducted among individuals diagnosed with type 2 diabetes mellitus at the Department of Geriatrics, İnönü University Turgut Özal Medical Center. All assessments will be administered in accordance with a rigorously standardized protocol. Eligible participants will include individuals aged 18 to 80 years who have had a confirmed diagnosis of type 2 diabetes mellitus for at least one year, are capable of comprehending and following verbal instructions in Turkish required for the study procedures, and provide written informed consent. All statistical analyses will be performed using IBM SPSS Statistics (v.29, Armonk, NY, USA) and JASP (v.0.18, Amsterdam, Netherlands).

Conditions

Diabetes Mellitus (DM)

Keywords

Diabetus Mellitus; Central sensitization; Temporal summation; Neuropathic pain

Outcome Measures

Primary Outcomes (1)

• Conditioned Pain Modulation (CPM) Test

  Assessment will be performed using an algometer. The algometer probe is positioned perpendicularly over the trapezius muscle. Pressure is increased at a rate of approximately 30 kPa/s. When the participant first perceives pain, the measurement is stopped and this value is recorded as PPT₁ (pre-test). Conditioning Stimulus (CS) - To evaluate ischemic pain, a blood pressure cuff is placed on the participant's non-dominant arm and rapidly inflated to 240 mmHg. The participant is then instructed to perform repeated hand-opening and closing exercises involving the distal arm (forearm muscles) for approximately 2 minutes. When the participant reports pain intensity as NRS ≥ 7/10, the conditioning stimulus is considered adequate. For the repeated PPT measurement, while the cuff remains inflated, PPT is measured again at the same location. This value is recorded as PPT₂ (post-test). The CPM effect is calculated using the formula: CPM effect = PPT₂ - PPT₁.

  Immediately before cuff inflation and immidiately after completion of the conditioning protocol

Secondary Outcomes (9)

• Central Sensitization Inventory (CSI)

  Baseline(First assesstment

• DN4 (Douleur Neuropathique)

  Baseline(First assesstment)

• Michigan Neuropathy Screening Instrument (MNSI)

  Baseline(First assesstment)

• Numerical Rating Scale (NRS)

  Baseline(First assesstment)

• Pain Catastrophizing Scale

  Baseline(First assesstment)

Study Arms (4)

Painful DPN Group

The study will include individuals aged 18-80 years who have been diagnosed with diabetic neuropathy, show a positive result on the MNSI-clinical assessment, and have a DN4 score of ≥4.This study is entirely observational and cross-sectional in nature, and no therapeutic intervention will be administered to the participants.

Painless DPN Group

The study will include individuals aged 18-80 years who have been diagnosed with diabetes mellitus, have a positive MNSI-clinical assessment, and a DN4 score of \<4. This study is entirely observational and cross-sectional in nature, and no therapeutic intervention will be administered to the participants.

Diabetic Control Group Without Diabetic Peripheral Neuropathy (DPN)

The study will include individuals aged 18-80 years who have been diagnosed with diabetes mellitus, have a negative MNSI-clinical assessment, and a DN4 score of \<4. This study is entirely observational and cross-sectional in nature, and no therapeutic intervention will be administered to the participants.

Healthy Control Group

The study will include individuals aged 18-80 years who do not have a diagnosis of diabetes mellitus, have a negative MNSI-clinical assessment, and a DN4 score of \<4. This study is entirely observational and cross-sectional in nature, and no therapeutic intervention will be administered to the participants.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Individuals aged 18-80 who have had a diagnosis of Type 2 diabetes for at least 1 year will be included in this study.

You may qualify if:

• Being between 18 and 80 years of age
• Having a diagnosis of Type 2 diabetes mellitus for at least 1 year
• Providing written informed consent to participate in the study

You may not qualify if:

• Non-diabetic causes of polyneuropathy (alcohol, chemotherapy, vitamin deficiencies, renal failure, hypothyroidism, etc.)
• Active ulcer, infection, or severe vascular insufficiency in the lower extremity
• Central nervous system disorders (stroke, multiple sclerosis, spinal cord injury, etc.)
• Skin lesions, dermatitis, wounds, or infection in the test areas (foot or forearm)
• Peripheral entrapment neuropathies or related radiculopathies (e.g., carpal tunnel syndrome, C7-C8 radiculopathy)
• Chronic widespread pain syndrome (fibromyalgia, etc.) or active flaring rheumatologic disease
• Dose change within the last 2-4 weeks in medications affecting pain modulation (gabapentinoids, SNRI/TCA, opioids, hypnotics, etc.)

Sponsors & Collaborators

• Inonu University: lead

Study Sites (1)

Inonu University Turgut Ozal Medical Center, Malatya

Malatya, Turkey (Türkiye)

Location

Related Publications (15)

• Granovsky Y, Shafran Topaz L, Laycock H, Zubiedat R, Crystal S, Buxbaum C, Bosak N, Hadad R, Domany E, Khamaisi M, Sprecher E, Bennett DL, Rice A, Yarnitsky D. Conditioned pain modulation is more efficient in patients with painful diabetic polyneuropathy than those with nonpainful diabetic polyneuropathy. Pain. 2022 May 1;163(5):827-833. doi: 10.1097/j.pain.0000000000002434.

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• Rabia Hacıhasanoğlu PK, Arzu Yıldırım,Seval Uslu, . Bir Sağlık Ocağına Başvuran Kronik Hastalığı Olan Bireylerde Anksiyete ve Depresyon 2010.

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• Öznur Tunca Yılmaz YY, Fatma Uygur, Naime Uluğ Tampa Kinezyofobi Ölçeği'nin Türkçe versiyonu ve test-tekrar test güvenirliği 2011.

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• Damla Karabay FT, Merve Keskin, Orhan Öztürk,Merve Kurt,Derya Özer Kaya. Ruminasyonun Tanınması ve Ağrı Deneyimi ve Fiziksel Aktivite ile İlişkisinin İncelenmesi: Geleneksel Derleme. 2023.

  BACKGROUND

• Robinson CL, Phung A, Dominguez M, Remotti E, Ricciardelli R, Momah DU, Wahab S, Kim RS, Norman M, Zhang E, Hasoon J, Orhurh V, Viswanath O, Yazdi C, Chen GH, Simopoulos TT, Gill J. Pain Scales: What Are They and What Do They Mean. Curr Pain Headache Rep. 2024 Jan;28(1):11-25. doi: 10.1007/s11916-023-01195-2. Epub 2023 Dec 7.

  PMID: 38060102 BACKGROUND

• Aktar Reyhanioglu D, Adiyaman SC, Bektas M, Bulut O, Ozgen Saydam B, Bayraktar F, Kara B. Validity and reliability of the Turkish version of the Michigan Neuropathy Screening Instrument. Turk J Med Sci. 2020 Jun 23;50(4):789-797. doi: 10.3906/sag-1906-63.

  PMID: 32178509 BACKGROUND

• Unal-Cevik I, Sarioglu-Ay S, Evcik D. A comparison of the DN4 and LANSS questionnaires in the assessment of neuropathic pain: validity and reliability of the Turkish version of DN4. J Pain. 2010 Nov;11(11):1129-35. doi: 10.1016/j.jpain.2010.02.003. Epub 2010 Apr 24.

  PMID: 20418179 BACKGROUND

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• Neblett R, Cohen H, Choi Y, Hartzell MM, Williams M, Mayer TG, Gatchel RJ. The Central Sensitization Inventory (CSI): establishing clinically significant values for identifying central sensitivity syndromes in an outpatient chronic pain sample. J Pain. 2013 May;14(5):438-45. doi: 10.1016/j.jpain.2012.11.012. Epub 2013 Mar 13.

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MeSH Terms

Conditions

Diabetes Mellitus; Neuralgia

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Zeynal Yasacı

  Inonu University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gamze Levent

CONTACT

+905455169598; uzunhasanoglugamze@gmail.com

Zeynal Yasacı

CONTACT

+905075409791; zeynal.yasaci@inonu.edu.tr

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor Lecturer

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: January 5, 2026
• Study Start: December 15, 2025
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2026
• Last Updated: January 5, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)