NCT03445403

Offset Analgesia as a Measure of Central Sensitization in Children

Completed NA Last updated 21 February 2021

What this trial tests

NA trial testing Offset analgesia in Chronic Pain Syndrome in 15 participants. Completed in 1 December 2020.

Timeline

1 April 2018

Primary endpoint
27 December 2019

1 December 2020

Quick facts

Lead sponsor	Boston Children's Hospital
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	double
Primary purpose	screening
Enrollment	15
Start date	1 April 2018
Primary completion	27 December 2019
Estimated completion	1 December 2020
Sites	1 location across United States

Drugs / interventions tested

• Offset analgesia

Conditions studied

• Chronic Pain Syndrome — all drugs for Chronic Pain Syndrome →
• Chronic Daily Headache — all drugs for Chronic Daily Headache →
• Functional Abdominal Pain Syndrome — all drugs for Functional Abdominal Pain Syndrome →
• Musculoskeletal Pain Disorder — all drugs for Musculoskeletal Pain Disorder →

Sponsor

Boston Children's Hospital

Who can join

Adults 10 to 17, any sex, with Chronic Pain Syndrome or Chronic Daily Headache. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.