Pain Inhibition in Patients With Rheumatoid Arthritis and Central Sensitivity Syndromes

Unraveling Impaired Pain Inhibition in Patients With Rheumatoid Arthritis and Central Sensitivity Syndromes: a Series of Experiments Targeting Brain Neurotransmission

Both patients with peripheral structural pathologies, like rheumatoid arthritis (RA)-patients, or patients with central sensitivity syndromes (CSS) suffer chronic pain. CSS are characterized by an increased responsiveness of central pain neurons. An impaired endogenous pain inhibition is already demonstrated in CSS. In the present study the investigators want to evaluate the efficacy of pain inhibition in response to physical stressors and whether the efficacy is opioid-mediated in two chronic pain populations (RA & CCS) compared to controls.

Therefore a triple-blinded randomized controlled trial (RCT) with cross-over design will be performed. The efficacy of wind-up of pain and spatial summation of pain is evaluated before and after a submaximal exercise, while the experimental group receives a selective serotonin reuptake inhibitor. Participants are 20 RA-patients and 20 CSS-patients, more specific patients with fibromyalgia and chronic fatigue syndrome, and 30 healthy controls. This way, the investigators analyze how pain inhibition reacts on different types of physical stressors in different pain patients and if pain inhibition is opioid-mediated.

Study Overview

• Status: Unknown
• Conditions: Arthritis, Rheumatoid; Fibromyalgia; Fatigue Syndrome, Chronic
• Intervention / Treatment: Drug: citalopram; Drug: 1 ml 0.9 % NaCl

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • University hospital Antwerp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Each study participant should be aged between 18 and 65 years. All three groups will be comparable for age, gender, education level and socioeconomic status; both patient groups will be comparable for illness duration.
• The Central Sensitivity Syndrome (CSS) group will comply with the diagnostic criteria for Fibromyalgia (FM) as defined by the American College of Rheumatology and the Centre of Disease Control criteria for Chronic Fatigue Syndrome (CFS).
• At the time of study participation, healthy control subjects cannot suffer any pain complaints. Sedentary is defined as a sedentary job and < 3 h moderate physical activity/week. Moderate physical activity is defined as activity demanding at least the threefold of the energy spent passively.
• Patients have to be able to cycle on a bicycle ergometer.

Exclusion Criteria:

• In order to preclude confounding factors, participants cannot be pregnant (pregnancy test) or until 1 year postnatal and will be asked to stop medication two weeks prior to study participation, not to undertake physical exertion, and to refrain from consuming caffeine, alcohol or nicotine on the day of the experiment. For ethical reasons, Rheumatoid arthritis(RA)-patients are able to take non-opioid pain medication as described in the 1st step of the World Health Organization analgesic ladder (Non-Steroidal Anti-Inflammatory Drugs and paracetamol).

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: selective serotonin reuptake inhibitor; intravenous, acute, 20mg/ml	Drug: citalopram; intravenous
PLACEBO_COMPARATOR: 1 ml 0.9 % NaCl	Drug: 1 ml 0.9 % NaCl; intravenous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain rates according to a visual analogue scale upon repeated pulses at pressure pain detection threshold intensity	Temporal summation is elicited with 10 pulses of the algometer at pressure pain detection threshold intensity on the dorsal surface of the right hand middle finger midway between the first and the second digital joints, and at the trapezius. Subjects are instructed to rate the pain level of the 1st, 5th and 10th pulse according to a visual analogue scale (VAS). To assess spatial summation an occlusion cuff inflated to a painful intensity and maintained at that level while repeated algometer pulses are administered and pain ratings are recorded again.	5 minutes before and after exercise

Collaborators and Investigators

• Sponsor: Vrije Universiteit Brussel
• Collaborators: University Hospital, Antwerp; Universiteit Antwerpen; Research Foundation Flanders; Artesis University College, Antwerp

Publications and helpful links

General Publications

• Meeus M, Hermans L, Ickmans K, Struyf F, Van Cauwenbergh D, Bronckaerts L, De Clerck LS, Moorken G, Hans G, Grosemans S, Nijs J. Endogenous pain modulation in response to exercise in patients with rheumatoid arthritis, patients with chronic fatigue syndrome and comorbid fibromyalgia, and healthy controls: a double-blind randomized controlled trial. Pain Pract. 2015 Feb;15(2):98-106. doi: 10.1111/papr.12181. Epub 2014 Feb 17.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ANTICIPATED): September 1, 2012

Study Registration Dates

• First Submitted: June 28, 2010
• First Submitted That Met QC Criteria: June 30, 2010
• First Posted (ESTIMATE): July 1, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2010
• Last Update Submitted That Met QC Criteria: June 30, 2010
• Last Verified: April 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Central Nervous System Diseases; Nervous System Diseases; Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Disease; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Syndrome; Arthritis; Arthritis, Rheumatoid; Fibromyalgia; Fatigue Syndrome, Chronic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: EudraCT 2010-020498-17