Offset Analgesia as a Measure of Central Sensitization in Children
Condition: Chronic Pain Syndrome; Chronic Daily Headache; Functional Abdominal Pain Syndrome; Musculoskeletal Pain Disorder; CRPS (Complex Regional Pain Syndromes)
MeSH terms: Musculoskeletal Pain; Rheumatic Diseases; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Headache Disorders; Collagen Diseases; Syndrome; Chronic Pain; Abdominal Pain; Somatoform Disorders
Study type: Interventional

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.
    

Detailed description: 
      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.
    

Intervention name(s): Offset analgesia
Intervention type(s): Other
Intervention description(s): 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.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: 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.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Screening
Keywords: Offset analgesia; Quantitive sensory testing