Childhood Adversity, Inflammatory Reactivity and Persistent Pain

NCT ID: NCT06127693

Last Updated: 2023-11-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 101 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-21
• Study Completion Date: 2023-09-20

Brief 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.

Conditions

Chronic Pain; Central Sensitisation; Immune Response; Adverse Childhood Experiences

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

Mild childhood adversity (control)

Score of 25-36 on the Childhood Trauma Questionnaire-short form.

Tetravalent Influenza Vaccine

Intervention Type: DRUG

All participants will receive the tetravalent influenza vaccine

High-frequency electrical stimulation

Intervention Type: BEHAVIORAL

All participants will receive High-frequency electrical stimulation

Moderate childhood adversity

Score of 37-67 on the Childhood Trauma Questionnaire-short form.

Tetravalent Influenza Vaccine

Intervention Type: DRUG

All participants will receive the tetravalent influenza vaccine

High-frequency electrical stimulation

Intervention Type: BEHAVIORAL

All participants will receive High-frequency electrical stimulation

Severe childhood adversity

Score of \>67 on the Childhood Trauma Questionnaire-short form.

Tetravalent Influenza Vaccine

Intervention Type: DRUG

All participants will receive the tetravalent influenza vaccine

High-frequency electrical stimulation

Intervention Type: BEHAVIORAL

All participants will receive High-frequency electrical stimulation

Interventions

Tetravalent Influenza Vaccine

All participants will receive the tetravalent influenza vaccine

Intervention Type: DRUG

High-frequency electrical stimulation

All participants will receive High-frequency electrical stimulation

Intervention Type: BEHAVIORAL

Other Intervention Names

flu vaccine

Eligibility Criteria

Inclusion Criteria

• Between the ages of 18 and 65 years old.

Exclusion Criteria

• Incompetence to consent and participate, e.g. acute psychosis or high suicide risk.
• Pregnancy,
• Electrical implants (e.g. pace-maker),
• Metal implants in the forearm,
• Tattoos on the forearm,
• Any visible injury or open wounds in the forearm,
• Known history of allergic reactions to vaccines,
• Has received the current season's influenza vaccine,
• Chronic pain (pain on most days for the past 3 months),
• Diabetes Mellitus,
• Peripheral vascular disease,
• Sensory impairment in the forearm, shoulder and lower back,
• Use of medication that could later skin sensitivity (e.g. analgesic medication, immune modulators, topical medical creams),
• Cardiovascular disorders,
• Medication that alters immune function (e.g. NSAIDs, steroids),
• Smoking habit,
• Febrile illness in the preceding 4 weeks.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Cape Town

OTHER

Sponsor Role: lead

Responsible Party

Victoria Madden

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Victoria J Madden, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cape Town

Locations

University of Cape Town

Cape Town, Western Cape, South Africa

Countries

South Africa

References

Bedwell GJ, Mqadi L, Kamerman P, Hutchinson MR, Parker R, Madden VJ. Inflammatory reactivity is unrelated to childhood adversity or provoked modulation of nociception. Pain. 2025 May 15:10.1097/j.pain.0000000000003658. doi: 10.1097/j.pain.0000000000003658. Online ahead of print.

Reference Type: DERIVED

PMID: 40372281 (View on PubMed)

Other Identifiers

HREC REF 560/2021

Identifier Type: -

Identifier Source: org_study_id