Offset Analgesia as a Measure of Central Sensitization in Children
| Status: | Enrolling by invitation |
|---|---|
| Conditions: | Migraine Headaches, Orthopedic, Psychiatric, Rheumatology, Pain, Pain |
| Therapuetic Areas: | Musculoskeletal, Neurology, Psychiatry / Psychology, Rheumatology, Orthopedics / Podiatry |
| Healthy: | No |
| Age Range: | 10 - 17 |
| Updated: | 6/14/2018 |
| Start Date: | May 15, 2018 |
| End Date: | July 1, 2019 |
Offset Analgesia as a Measure of Central Sensitization in Children With Chronic Pain Disorders
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.
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.
Specific Aims/Objectives To date, OA has not been evaluated in pediatric chronic pain
disorders. In the current study, the investigators plan to measure OA responses in a
population of common pediatric pain disorders. The primary objective of this study is to
determine if OA paradigm can detect impairment of central inhibitory modulation pathways in
subgroups of chronic pain disorders in children and adolescents. The investigators
hypothesize that chronic pain in children and adolescents results from central sensitization
and impaired central inhibitory modulation of pain and thus children with chronic pain
disorders will have a decreased OA response compared with healthy controls. If the results of
this study are positive, this testing paradigm could be a valuable objective marker in
examining the efficacy of pharmacological and/or rehabilitative treatment modalities in
reversing or alleviating central sensitization-induced pain in children with chronic pain
disorders. Additionally, if existing self-report questionnaires, Pain Sensitivity
Questionnaire (PSQ) and Central Sensitivity Inventory, correlate with the magnitude of offset
analgesia observed, they could be used to screen for central sensitization in high volume and
busy clinical settings.
Aim 1: To determine if children with common chronic pain disorders, including musculoskeletal
pain, complex regional pain syndrome, functional abdominal pain and chronic headaches
demonstrate impaired ability to actuate central descending inhibitory function as measured by
a test of offset analgesia.
To accomplish this aim, the investigators will compare 30 children with common chronic pain
disorders with 30 age and sex matched controls. Power will be 80% to detect a 20% or larger
difference in the change in self-reported pain scores as a result of the dynamic heat pain
test stimulus between the two groups using a Student t-test (nQuery Advisor version 7.0,
Statistical Solutions, Cork, Ireland).
Aim 2: To determine if the Pain Sensitivity Questionnaire (PSQ) and/or Central Sensitization
Inventory (CSI) can serve as screening tools for assessment of central sensitization i.e.,
impairment of central descending inhibitory function in children with common chronic pain
disorders.
To accomplish this aim investigators will correlate scores on the above scales with the
magnitude of offset analgesia using Pearson correlations in 30 children with chronic pain
disorders and 30 healthy age and sex-matched controls. The investigators hypothesize that the
magnitude of OA will correlate with either PSQ, CSI or both thus these questionnaires would
serve as assessment tools for central sensitization in children with common chronic pain
disorders in clinical setting. The Mann-Whitney U-test will be applied to compare medians and
interquartile ranges on the PSQ and CSI between the chronic pain and healthy control groups.
In addition, investigators will identify individuals who show a decrease in VAS pain scores
after the dynamic test stimulus of at least 20% (responders) and will assess whether PSQ and
CSI can predict responders and non-responders using a receiver operating characteristic (ROC)
curve approach with area under the curve (AUC) to measure how well pain perception and
central sensitization assessment tools can help to identify responders and non-responders.
disorders. In the current study, the investigators plan to measure OA responses in a
population of common pediatric pain disorders. The primary objective of this study is to
determine if OA paradigm can detect impairment of central inhibitory modulation pathways in
subgroups of chronic pain disorders in children and adolescents. The investigators
hypothesize that chronic pain in children and adolescents results from central sensitization
and impaired central inhibitory modulation of pain and thus children with chronic pain
disorders will have a decreased OA response compared with healthy controls. If the results of
this study are positive, this testing paradigm could be a valuable objective marker in
examining the efficacy of pharmacological and/or rehabilitative treatment modalities in
reversing or alleviating central sensitization-induced pain in children with chronic pain
disorders. Additionally, if existing self-report questionnaires, Pain Sensitivity
Questionnaire (PSQ) and Central Sensitivity Inventory, correlate with the magnitude of offset
analgesia observed, they could be used to screen for central sensitization in high volume and
busy clinical settings.
Aim 1: To determine if children with common chronic pain disorders, including musculoskeletal
pain, complex regional pain syndrome, functional abdominal pain and chronic headaches
demonstrate impaired ability to actuate central descending inhibitory function as measured by
a test of offset analgesia.
To accomplish this aim, the investigators will compare 30 children with common chronic pain
disorders with 30 age and sex matched controls. Power will be 80% to detect a 20% or larger
difference in the change in self-reported pain scores as a result of the dynamic heat pain
test stimulus between the two groups using a Student t-test (nQuery Advisor version 7.0,
Statistical Solutions, Cork, Ireland).
Aim 2: To determine if the Pain Sensitivity Questionnaire (PSQ) and/or Central Sensitization
Inventory (CSI) can serve as screening tools for assessment of central sensitization i.e.,
impairment of central descending inhibitory function in children with common chronic pain
disorders.
To accomplish this aim investigators will correlate scores on the above scales with the
magnitude of offset analgesia using Pearson correlations in 30 children with chronic pain
disorders and 30 healthy age and sex-matched controls. The investigators hypothesize that the
magnitude of OA will correlate with either PSQ, CSI or both thus these questionnaires would
serve as assessment tools for central sensitization in children with common chronic pain
disorders in clinical setting. The Mann-Whitney U-test will be applied to compare medians and
interquartile ranges on the PSQ and CSI between the chronic pain and healthy control groups.
In addition, investigators will identify individuals who show a decrease in VAS pain scores
after the dynamic test stimulus of at least 20% (responders) and will assess whether PSQ and
CSI can predict responders and non-responders using a receiver operating characteristic (ROC)
curve approach with area under the curve (AUC) to measure how well pain perception and
central sensitization assessment tools can help to identify responders and non-responders.
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
We found this trial at
1
site
Click here to add this to my saved trials
