Offset Analgesia as a Measure of Central Sensitization in Children

NCT03445403 | Completed

• 1 other identifier: P00025596
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Pediatric chronic pain disorders are common and consequential in Western societies, occurring in 25-80% of population-based samples with a median prevalence of 11-38% and significant pain-related disability in 3-5% of these children. Pediatric chronic pain disorders have a negative impact on many aspects children's lives including mobility, night sleep, school attendance, peer relationships, family functioning, and overall quality of life. Parents caring for these children risk loss of parental earnings, and these disorders place a high financial burden on healthcare. In a nationally representative sample in the United States, costs related to health care were significantly higher ($1,339 per capita) for children with chronic pain disorders compared to children with common pediatric health conditions of ADHD, asthma and obesity. In children with clinical chronic pain conditions, such as daily headaches or fibromyalgia, chronic pain is presumably a persistent state of an overly excitable nervous system. This phenomenon known as central sensitization is characterized by excessive pain sensitivity that occurs in response to non-painful stimuli, such as light touch or contact with clothing, and slightly painful stimuli, such as a light pinprick. This hypersensitivity results from peculiar changes in the working of the central nervous system, including the spinal cord and brain, and leads to unusual intensification of pain that is out of proportion to the inciting stimulus. For example, light touch from clothing on the skin is perceived as intensely painful. Central sensitization is also thought to contribute to the spreading of pain to other body sites in several chronic pain disorders. In chronic pain disorders, the function of the central descending inhibitory modulating system is likely impaired and is traditionally measured by a phenomenon identified as "conditioned pain modulation (CPM)" and more recently measured by a phenomenon of "offset analgesia" (OA). The OA test is more robust than the CPM test and likely more acceptable to most patients, especially children, because it is shorter in duration and uses a more tolerable painful stimulus. Compared to CPM, the OA test is more tolerable because it is conducted using a painful test stimulus that is less than the maximal (suprathreshold). Additionally, the time of exposure to the painful stimulus is significantly shorter, a few seconds, in the OA test compared to CPM. The central descending inhibitory pathway that modulates pain as tested by OA is functional and mature in healthy children as young as 6 year of age, but it has yet to be investigated in children with chronic pain disorders. The investigators plan to test OA responses in a population of common pediatric pain disorders with overlapping symptomology attributed to central sensitization (such as chronic musculoskeletal pain, chronic abdominal pain and chronic headaches and chronic regional pain syndromes) and compare their responses with an age- and sex-matched control group. The characteristics of OA responses in each group will allow for assessment of the presence or absence of central sensitization as a mechanism driving the persistent, abnormal pain in a subgroup of these chronic pain disorders. The investigators hypothesize that central sensitization is the potential contributory mechanism of the central nervous system heightened sensitivity to two testing stimuli of painful (moderate heat discomfort sensation) and non-painful (warmth sensation) in children with chronic pain disorders. These types of sensations mimic those that children would be expected to experience their natural environment during typical activities of daily living such as showering/bathing in warm water or hand washing. Additionally, the Pain Sensitivity Questionnaire (PSQ) and Central Sensitization Inventory (CSI) will be used as clinical screening tools for subjective report of sensitization symptoms, and are simple and easy to administer in a clinical setting. The investigators hypothesize that these measures will correlate with the objective offset analgesia responses thus allowing for assessment of central sensitization in children with chronic pain disorders. These tests are advantageous because they are feasible to perform rapidly in a clinic setting and have utility for measurement of patient responses to therapeutic interventions. If this concept is supported by this study, future studies could utilize OA to examine the effects of various pharmacological and physical interventions used to manage children with chronic pain disorders including intensive interdisciplinary rehabilitation or specific interventions such as aerobic exercise, which likely modulates pain via similar mechanisms.

Conditions

Chronic Pain Syndrome; Chronic Daily Headache; Functional Abdominal Pain Syndrome; Musculoskeletal Pain Disorder; CRPS (Complex Regional Pain Syndromes)

Keywords

Offset analgesia; Quantitive sensory testing

Outcome Measures

Primary Outcomes (1)

• Response to Offset analgesia stimulus

  A reduction in self-reported pain intensity when a moderate heat-pain stimulus is applied for 5 seconds, raised by 1 degree C for 5 seconds, reduced by 1 degree C, and held for 20 seconds. During all tests, patients will rate heat pain intensity continuously in real time using the linear, electronic visual analogue scale (eVAS). Patients will use their dominant hand to operate sliding knob of the eVAS with the following two anchors on 0 to 100 mm line. The left endpoint designated as "no pain sensation" (0 mm) and the right endpoint as "most intense pain sensation imaginable" (100 mm).

  outcome will be observed in a single session over one hour period

Secondary Outcomes (4)

• Response to a Controlled Stimulus

  outcome will be observed in a single session over one hour period

• Response to a Constant Stimulus

  outcome will be observed in a single session over one hour period

• Pain sensitivity questionnaire

  outcome will be observed in a single session over one hour period

• Central sensitization inventory

  outcome will be observed in a single session over one hour period

Study Arms (2)

Chronic pain disorders

EXPERIMENTAL

Administration of offset analgesia and control and constant paradigms using moderate heat pain as determined by the individual subject reporting of 50 mm on a visual analog pain scale of 0-100 mm.

Other: Offset analgesia

Healthy controls

ACTIVE COMPARATOR

Administration of offset analgesia and control and constant paradigms using moderate heat pain as determined by the individual subject reporting of 50 mm on a visual analog pain scale of 0-100 mm.

Other: Offset analgesia

Interventions

Offset analgesia OTHER

Exposure to a moderate heat-pain stimulus applied for 5 seconds, raised by 1 degree C for 5 seconds, reduced by 1 degree C, and held for 20 seconds using a computerized paradigm in order to evoke endogenous pain modulation.

Chronic pain disorders; Healthy controls

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Patients experiencing chronic pain defined as pain persisting for 3 months.
• Ages 10-17 years, both sexes and all races and ethnic groups.
• Patients with moderate pain rated as 5/10 and greater on a numeric rating scale of 0 to 10 points.
• English speaking.
• If patients are taking medications such as psychotropic (e.g., SSRI), opioid, anxiolytics or anticonvulsive drugs for pain such as gabapentinoids, they must be on stable doses for at least one week.
• Stable anxiety and depression.

You may not qualify if:

• Intermittent pain or pain of less than 3-month duration.
• Allodynia in the upper extremities
• Patients with poor understanding of English language or developmental disorders that affect the ability to reliably rate pain, read questionnaires and follow study instructions.
• Children and adolescents with a history of central nervous system, heart, kidney, liver, and respiratory system diseases.
• Psychiatric disorders such as conversion, bipolar disorder or psychosis.

Sponsors & Collaborators

• Boston Children's Hospital: lead

Study Sites (1)

Boston Children's Hospital

Waltham, Massachusetts, 02453, United States

Location

MeSH Terms

Conditions

Headache Disorders; Collagen Diseases; Complex Regional Pain Syndromes

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autonomic Nervous System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: During offset analgesia testing, participants will be exposed to 3 heat pain paradigms: a constant heat stimulus, the offset analgesia paradigm, and a control paradigm. The participants will not be aware of the direction/pattern of temperature changes or which paradigm is being applied. Participants will not be allowed to view the computer screen so that it would not influence their response. The statistician will be unaware of the participants allocation of children with chronic pain vs. control
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Clinical Director, Mayo Family Pediatric Pain Rehabilitation Center, Professor of Anesthesiology Harvard Medical School

Model Details: Response to a moderate heat pain \[defined as a heat stimulus producing pain rated at 50mm on a scale of 0-100 mm\] applied the the skin of the forearm using a paradigm known as offset analgesia will be compared in children with chronic pain disorders and healthy, age and sex matched controls.

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: February 26, 2018
• Study Start: April 1, 2018
• Primary Completion: December 27, 2019
• Study Completion: December 1, 2020
• Last Updated: February 21, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)