Central Sensitization in Vitamin D Deficiency

Study Overview
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Brief Summary
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The purpose of this study is to investigate the presence of central sensitization in vitamin D deficiency and its effect on cutaneous silent period, pain, and quality of life. The secondary purpose of the study is to investigate whether a change in cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life after vitamin D replacement.

Detailed Description
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Vitamin D deficiency is a pandemia. Main causes of this is insufficient exposure to sunlight. Vitamin D deficiency is related to conditions like various cancers, autoimmune diseases, hypertension and growth retardation in children (1). International Association for the study of pain has defined pain as An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. (2). Pain lasting longer than 3 months has been deemed as chronic pain (3). Vitamin D deficiency influences various types of pain, including chronic pain (4,5,6,7). Vitamin D influences the musculoskeletal system via the calcium-phosphorus metabolism and the receptors found in skeletal muscle cells (8). Vitamin D deficiency has been shown to decrease muscle strength, the this decrease in proximal muscles affect postural stability and can increase falls. Vitamin D deficiency also causes problems in bone mineralization, causing isolated or widespread pain in muscles, bones and joints. These patients end up getting wrong diagnoses such as fibromyalgia, osteoarthritis, inflammatory arthritis, and chronic fatigue syndrome (1,7). Vitamin D deficiency causes hyperinnervation and hypersensitivity on nerves and cause pain to be felt more intensely (5). In a normal skeletal muscle, during an isometric contraction, a number of motor unit will be activated. These motor units produce a stable electromyography pattern and keep their own frequencies during contraction. If the nerve, tendon or a cutaneous nerve nearby is stimulated, electromyographic activity is disrupted and a bioelectric silence occurs. This is called cutaneous silent period (CSP). It is an inhibitory spinal reflex and its afferents consist of A-delta nerve fibers. In various studies, CSP has been shown to be clinically beneficial in conditions like peripheral neuropathy, syringomyelia, Parkinson's disease, restless leg syndrome and fibromyalgia. von Känel R et al. has investigated the effect of vitamin D deficiency on widespread pain index (WPI) and symptom severity score (SSS) and found out that it increases central sensitivity (8). In thei study, thy did not utilize any electrophysiologic objective measurements. Akyüz et al. have investigated the effect of vitamin D deficiency on chronic pain and nerve conduction studies; they have shown that vitamin D is correlated with various nerve conduction parameters while these parameters do not change after replacement (9,10). Patients with vitamin D deficiency and healthy controls with normal vitamin D levels will be compared in terms of cutaneous silent period parameters, pain severity and neuropathic sensitization and quality of life. Cutaneous silent period parameters (duration and latency ), The Leeds Assessment of Neuropathic Symptoms & Signs and Nottingham Health Profile will be used for the assessments. Patients with vitamin D deficiency will receive vitamin D supplementation therapy. Before and after therapy, cutaneous silent period parameters, LANSS scores and Nottingham Health Profile will measured before and 8 weeks after starting vitamin D supplementation therapy.

Official Title
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Central Sensitization in Vitamin D Deficiency and Effect of Vitamin D Replacement on Cutaneous Silent Period

Conditions
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Vitamin D Deficiency, Central Sensitisation

Intervention / Treatment
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* Dietary Supplement: vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Presence of widespread pain Presence of vitamin D deficit Exclusion Criteria: Any contraindication of performing silent cutaneous period Any contraindication for vitamin d use Presence of conditions that affect cutaneous silent period like the presence of carpal tunnel syndrome and polyneuropathies Defective peripheric autonomic nervous system findings Not being able to write and read Not being able to communicate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional Arm<br>Patients with vitamin D deficiency will receive vitamin D replacement therapy. Before and after therapy, cutaneous silent period will be measured from each upper extremity and latencies will be recorded. Their LANSS scores and Notthingham Health Profile will be recorded before and after treatment. | Dietary Supplement: vitamin D<br>* Vitamin D replacement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cutaneous silent period latency (ms) | the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve | 8 weeks | 
| cutaneous silent period duration (ms) | the brief interruption in voluntary contraction that follows strong electrical stimulation (painful) of a cutaneous nerve | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual analog scale (VAS) of pain | line from 0: no pain to 10:worst pain | 8 weeks | 
| Leeds assessment of neuropathic symptoms and signs (LANSS) | Reduction of pain related to central sensitization. LANSS scale ⩾ 12 refers to Neu- neuropathic sensitization | 8 weeks | 
| The Nottingham Health Profile (NHP) | The Nottingham Health Profile is intended for primary health care, to provide a brief indication of a patient's perceived emotional, social and physical health problems. The number of questions answered yes in each subgroup is divided by the total number of questions in the same subgroup and the result is multiplied by 100. Each subgroup has a value of between 0 and 100, with 100 points being considered the best general QoL for the calculated subgroup and 0 points being considered as the worst QoL for the same subgroup. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Central Sensitisation, Cutaneous Silent Period, Vitamin D Deficiency