Investigation of Central Sensitization Frequency and Related Factors in Axial Spondyloarthritis Patients

Axial Spondyloarthritis Clinical Trial

Official title:

The Clinical and the Functional Impact of Central Sensitization On Patients With Axial Spondyloarthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04485078
• Other study ID #: 09.2019.695
• Status: Completed
• Start date: October 20, 2019
• Est. completion date: April 18, 2020

Study information

• Verified date: July 2020
• Source: Marmara University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases that characterized with spinal involvement. AxSpA is one of the most common rheumatic diseases and chronic pain and morning stiffness are the main complaints of these patients. Central sensitization is defined as increased response to normal or sub-threshold stimuli of central nervous system and its close relationship with many rheumatological diseases has been demonstrated in several studies. Pain in axSpA patients is generally considered as a result of increased inflammatory burden and structural changes, However, failure to adequate analgesia in every patient whose inflammation is suppressed with anti-inflammatory treatment suggests new pain mechanisms. Central sensitization (CS) is one of these mechanisms and its recognition is only possible by detailed evaluation of the patient. There is no method for the diagnosis of central sensitization is accepted as a gold standard. clinical scales and quantitative sensory testing (QST) widely is used for this purpose widely. The most commonly used QST types include pressure pain threshold (PPT), temporal summation (TS) and conditioned pain modulation (CPM). The well-known scale used for the evaluation of central sensitization is the Central Sensitization Inventory , developed by Mayer et.al in 2011 for detect central sensitization in chronic pain patients. The aim of this study is to evaluate the frequency of central sensitization (CS) in patients with axSpA by means of clinical scales and quantitative sensory testing (QST), to examine related comorbidities and the parameters associated with the development of sensitization in these patients.

Description:

The term axial spondyloarthritis (axSpA) describes a group of chronic inflammatory diseases that characterized with spinal involvement. AxSpA is one of the most common rheumatic diseases and chronic pain and morning stiffness are the main complaints of these patients. Central sensitization (CS) is defined as increased response to normal or sub-threshold stimuli of central nervous system and its close relationship with many rheumatological diseases has been demonstrated in several studies. However, data associated with central sensitization in axSpA patients is very limited. The quantitative sensory testing (QST) is commonly used for detection hyperalgesia and allodynia those are accepted main findings in sensitized patients. The most commonly used QST types include pressure pain threshold (PPT), temporal summation (TS) and conditioned pain modulation (CPM).Pressure pain threshold measurement is frequently used to show local / generalized sensitivity increase in patients who develop pain sensitization. For this purpose, the pain response of superficial or deep tissue can be evaluated through mechanical device called algometer. The algometer probe was placed vertically in the each selected point and pressure was increased until the participant reporting pressure became painful. The first pressure value at which pain is felt is considered the PPT of that point. TS is defined as a progressive increase in pain response with repetitive painful stimuli. This condition is also known as wind-up phenomenon and play a role to development CS. CPM, known as one of the main mechanisms of endogenous analgesia, is based on the principle that pain perception can be reduced with painful stimulus applied to different areas according to the "pain inhibits pain" model. In the CPM testing, it is aimed to investigate the modulator effect of two different painful stimuli on each other. The diagnosis of CS can be made with QST or with Central Sensitization Inventory (CSI). The aim of this study is to evaluate the frequency of central sensitization (CS) in patients with axial spondyloarthritis (AxSpA) by means of clinical scales and quantitative sensory testing (QST), to examine related comorbidities and the parameters associated with the development of sensitization in these patients. The patients with AxSpa and healthy controls will be included in this study. QST which consists of pressure pain threshold (PPT), temporal summation (TS) and conditioned pain modulation (CPM) will be applied to the patient and control groups. Disease activity (BASDAI), functional status (ASQoL, ILBPDI), sleep quality (PSQI), pain (VAS pain), depression (BDI) and fatigue (FSS) will be assessed. Fibromyalgia (FIRST) and other comorbidities will be investigated. Patients will be divided as the ones with and without CS according to the central sensitization inventory (CSI) and the results will be compared. After data collection, analysis will be performed with the appropriate statistical method

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: April 18, 2020
• Est. primary completion date: February 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

Diagnosed with axSpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria Aged between 18-65 years

Exclusion Criteria:

Had an other rheumatic diseases, peripheral vascular disease, peripheral neuropathy and spine disease (e.g., symptomatic herniated disc, spinal stenosis), Using centrally acting pain medications (e.g., pregabaline, duloxetine, opioids) or glucocorticoids (>10 mg prednisone or its equivalent) within 3 months of study enrollment

The exclusion criteria of the control grup were same as that of the patients.

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• Central Sensitisation
• Spondylarthritis

Intervention

Diagnostic Test:
• Pressure pain threshold
The PPT assessments of spine will be performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The regional PPT scores will be composed from sum of all PPT values for related segments at spine. The sacroiliac PPT scores will be obtained bilaterally from four measurement points; the first point is located 1 cm medially and caudally from spina iliaca posterior superior (SIPS) and 3 more laterally, medially and cranially.The left trapezius muscle will be used to evaluate distant control point .The 1 cm2 algometer probe will be placed vertically in the each selected point and pressure will be increased with 0.1 kg/sc until the participant reporting pressure became painful. The pressure value at which the pain is first felt will be accepted as the PPT of that point.
• Temporal summation
TS will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 levels at spine with manuel algometer. TS scores will be calculated for each spine level as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will be asked to rate their pain using on a 0 to 10 visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds. The point that is located 1 cm medially and caudally from SIPS was used for SI joint TS measurement on both sides.
• Conditioned pain modulation
First stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS as called a test stimulus. After that the right hand of the patient will be immersed in 70C water for 20 seconds to create a conditioning stimulus. Second test stimulus with the same intensity of first one will be applied to trapezius after the conditioning stimulus and patients will be asked to rate their pain. If the patients cannot hold their hand in the water for 20 seconds, the test stimulus will be applied immediately after the patients removed their hands out of water. The ratio between the first and second VAS values multiplied by 100 will be defined as CPM score
• Central Sensitization Inventory
Standardized questionnaire to determine the level of central sensitization

Other:
• Bath Ankylosing Spondylitis Disease Activity Index
Standardized questionnaire to determine the level of disease activity in AxSpa patients
• Ankylosing Spondylitis Quality of Life
Standardized questionnaire to investigate the quality of life in AxSpa patients
• Istanbul Low Back Pain Disability Index
Standardized questionnaire to investigate the disability
• Beck Depression Inventory
Standardized questionnaire to investigate the depression
• Fatigue Severity Scale
Standardized questionnaire to investigate the fatigue
• Pittsburgh Sleep Quality Index
Standardized questionnaire to investigate the sleep quality and disturbance
• Fibromyalgia Rapid Screening Tool
Standardized questionnaire to detect fibromyalgia
• Visual analogue scale
global pain score on a 0 to 10

Locations

Country	Name	City	State
Turkey	Feyza Nur YUCEL	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Marmara University

Country where clinical trial is conducted

Turkey, 

References & Publications (9)

Arendt-Nielsen L, Graven-Nielsen T, Svensson P, Jensen TS. Temporal summation in muscles and referred pain areas: an experimental human study. Muscle Nerve. 1997 Oct;20(10):1311-3. — View Citation

Doward LC, Spoorenberg A, Cook SA, Whalley D, Helliwell PS, Kay LJ, McKenna SP, Tennant A, van der Heijde D, Chamberlain MA. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis. Ann Rheum Dis. 2003 Jan;62(1):20-6. — View Citation

Duruöz MT, Özcan E, Ketenci A, Karan A. Development and validation of a functional disability index for chronic low back pain. J Back Musculoskelet Rehabil. 2013;26(1):45-54. doi: 10.3233/BMR-2012-00349. — View Citation

Middlebrook N, Heneghan NR, Evans DW, Rushton A, Falla D. Reliability of temporal summation, thermal and pressure pain thresholds in a healthy cohort and musculoskeletal trauma population. PLoS One. 2020 May 29;15(5):e0233521. doi: 10.1371/journal.pone.02 — View Citation

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. 20 — View Citation

Rolke R, Baron R, Maier C, Tölle TR, Treede RD, Beyer A, Binder A, Birbaumer N, Birklein F, Bötefür IC, Braune S, Flor H, Huge V, Klug R, Landwehrmeyer GB, Magerl W, Maihöfner C, Rolko C, Schaub C, Scherens A, Sprenger T, Valet M, Wasserka B. Quantitative — View Citation

Strand V, Singh JA. Patient Burden of Axial Spondyloarthritis. J Clin Rheumatol. 2017 Oct;23(7):383-391. doi: 10.1097/RHU.0000000000000589. Review. — View Citation

van Leeuwen RJ, Szadek K, de Vet H, Zuurmond W, Perez R. Pain Pressure Threshold in the Region of the Sacroiliac Joint in Patients Diagnosed with Sacroiliac Joint Pain. Pain Physician. 2016 Mar;19(3):147-54. — View Citation

Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Landau R, Marchand S, Matre D, Nilsen KB, Stubhaug A, Treede RD, Wilder-Smith OH. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015 Jul;19(6) — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Sensitization Inventory (CSI)	25 somatic and psychosocial symptoms, which are frequently found in patients with central sensitization in part A, are questioned. In part B, the presence of diseases whose relationship with central sensitization is well defined is questioned in the patient without participating in scoring. Central sensitization is assumed in patients who score 40 or more over 100 points.	3 months
Secondary	Pressure pain threshold	The spinal hyperalgesia will be evaluated from C3 and C7 (cervical); T6 and T2 (thoracic); L3 and L5 (lumbar) levels. The PPT assessments of these levels were performed over the spinous process and 2 cm right and left side of the corresponding spinous process. The sacroiliac PPT scores were obtained from four measurement points [1]. Trapezius muscle will be used to evaluate distant control point	3 months
Secondary	Temporal summation	TS scores will be evaluated over the trapezius muscle, sacroiliac joints, C7, T6, and L3 spine. TS scores will be calculated for each spine as the sum of three values which measured over the spinous process and 2 cm right and left side of corresponding level. In the evaluation of TS, a pressure as much the PPT value of each point will be applied with pain pressure algometer ten times with a 1-second interstimulus interval. Patients will ve asked to rate their pain using visual analogue scale (VAS) at 0, 5, and 10 seconds. TS will be calculated by subtracting the rating at 0 seconds from the rating at 10 seconds	3 months
Secondary	Conditioned pain modulation	For the assessment of conditioned pain modulation (CPM), first stimulus will be applied to trapezius with the pressure that induced a pain intensity of 4 point on a 10 point VAS. After that the right hand of the patient will be immersed in 7 degrees Celcius water for 20 seconds to create a conditioning stimulus. Second stimulus with the same intensity of first one was applied to trapezius after the conditioning stimulus and patients asked to rate their pain. The ratio between the first and second VAS values will be defined as CPM	3 months
Secondary	VAS pain	The patients pain severity will be evaluated with a 10-cm horizontal visual analogue scale (VAS) ranging from "0 cm" (no discomfort) to "10 cm" (worst imaginable)	3 months
Secondary	Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	BASDAI is one of the most frequently used scales for determining disease activity in axSpA patients and includes questions to evaluate the patient's axial and peripheral symptoms, fatigue and morning stiffness. The questionnaire consists of 10 questions in total and is interpreted in favor of disease activity of 4 points or more.	3 months
Secondary	Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL)	This scale was developed by Doward et.al in 2003 and consists of 18 questions in total. Each question is answered as yes or no, and the total score is calculated by evaluating the yes answer as 1 and no as 0. It is frequently used in clinical practice because it helps to evaluate the effects of the disease and determine treatment strategies in patients diagnosed with AxSpa.	3 months
Secondary	Istanbul Low Back Pain Disability Index (ILBPDI)	This scale was developed for assessing the severity of disability in chronic low back pain patients by Duruöz et.al in 2013. This scale consists of 18 questions in the form of a Likert scale that evaluates the limitation of daily life activities of patients in the last month.	3 months
Secondary	Beck Depression Inventory (BDI)	This questionnaire consists of 21 questions, each with four options. Scoring is interpreted as 0-9 normal, 10-18 mild depression, 19-29 moderate depression and 30-63 points as severe depression.	3 months
Secondary	Fatigue severity scale (FSS)	The FSS includes 9 questions included in order to determine the negative effects of fatigue intensity and fatigue on daily life activities in the last week. If the score more than 6.1, this is interpreted in favor of chronic fatigue syndrome.	3 months
Secondary	Pittsburgh Sleep Quality Index (PSQI)	This scale is designed for quantitative measurement of sleep quality and consists of 24 questions in total. The questions are divided into 7 sections those included sleep disturbance-related symptoms. High scores are associated with poor sleep quality.	3 months
Secondary	Fibromyalgia Rapid Screening Tool	This questionnaire is consisted of 6 questions in which fibromyalgia-related clinical parameters are investigated. The patient scoring at least 5 points is considered has fibromyalgia.	3 months

External Links

•   IASP terminology