Childhood Adversity, Inflammatory Reactivity and Persistent Pain
Condition: Chronic Pain; Central Sensitisation; Immune Response; Adverse Childhood Experiences
MeSH terms: Chronic Pain
Study type: Observational

Summary: 
      The goal of this observational study is to investigate how adverse experiences during
      childhood are linked to people experiencing persistent pain and fatigue in adulthood.

      The questions the investigators aim to answer are:

        1. Does participant-reported childhood adversity predict levels of IL-6 and TNF-α after in
           vitro provocation of whole blood using endotoxin?

        2. Do levels of IL-6 and TNF-α after in vitro immune provocation using endotoxin predict
           vulnerability to persistent pain and fatigue after in vivo immune provocation
           (tetravalent influenza vaccine)?

        3. Do levels of IL-6 and TNF-α after in vitro immune provocation using endotoxin predict
           vulnerability to persistent pain and fatigue after in vivo neural provocation?

      For this study, the investigators will recruit and enrol 96 healthy human adults (18 - 65
      years old) with a range of adverse experiences during childhood. Participants will attend 2
      study sessions during which the investigators will take a sample of blood, assess pressure
      pain threshold before and after cold water immersion, assess heart rate variability, and
      assess the surface area of secondary skin hypersensitivity after electrical stimulation. At
      the end of the first session, participants will receive the influenza vaccination.
    

Detailed description: 
      Background

      Adverse experiences during childhood (childhood adversity) are associated with an increased
      risk of persistent pain and fatigue in adulthood. While the physiological relationships that
      link childhood adversity, persistent pain, and fatigue are unclear, all three factors are
      each associated with heightened innate immune and neural responses in adulthood. As such,
      neuroimmune interactions could underlie the relationship between childhood adversity,
      persistent pain, and fatigue, although the balance between the immune and neural influences
      likely varies across individuals.The investigators hypothesise that childhood adversity
      influences persistent pain and fatigue by priming: 1) immune, 2) neural, or 3) both systems,
      within an individual. Although previous studies have examined either immune or neural
      processes representing vulnerability to persistent pain and fatigue, the investigators are
      not aware of any study that has investigated both systems in the same cohort.

      Methods

      96 healthy adult humans with a range of childhood adversity history will undergo
      psychophysical testing before and after in vivo neural provocation (high frequency electrical
      stimulation) and, separately, immune provocation (influenza vaccine). Study proxies for
      vulnerability to persistent pain are surface area of secondary skin hypersensitivity induced
      by neural provocation and change in conditioned pain modulation after immune provocation; the
      proxy for vulnerability to fatigue is heart rate variability 24h after immune provocation.
      Immune responsiveness is represented by IL-6 and TNF-α levels in supernatant after in vitro
      lipopolysaccharide provocation of whole blood. The investigators hypothesise that levels of
      IL-6 and TNF-α after in vitro immune provocation will be positively associated with the area
      of secondary skin hypersensitivity after in vivo neural provocation, and negatively
      associated with conditioned pain modulation after in vivo immune provocation.
    

Intervention name(s): Tetravalent Influenza Vaccine; High-frequency electrical stimulation
Intervention type(s): Drug; Behavioral
Intervention description(s): All participants will receive the tetravalent influenza vaccine; All participants will receive High-frequency electrical stimulation
Other intervention name(s): flu vaccine
Intervention MeSH terms: Vaccines
Observational model: Other
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The investigators will recruit healthy adult volunteers (≥18 and ≤ 65 years old) with a
        range of childhood trauma. All interested volunteers will complete the Childhood Trauma
        Questionnaire-Short form. The investigators will use the total score on the questionnaire
        to recruit specifically for a varied range in childhood adversity history and enrol
        participants into three similarly sized groups: 1) minimal childhood adversity (control)
        (score 25-36), 2) low-moderate childhood adversity (score 37-67), and 3) severe childhood
        adversity (score > 67). The investigators will enrol volunteers into each group using a
        'first to qualify, book, and attend the testing sessions' approach, with the goal of
        achieving similar group sizes. Some groups may fill up faster than others.
      
Biospecimen description: 
      Blood plasma
    
Keywords: Secondary hyperalgesia; Pain; Innate immune response; Adverse childhood experiences; Conditioned pain modulation