Why Does Acute Post Whiplash Injury Pain Transform Into Chronic Pain?

Why Does Acute Post Whiplash Injury Pain Transform Into Chronic Pain? Multi-modal Assessment of Risk Factors and Predictors of Pain Chronification

Why does acute post whiplash injury pain transform into chronic pain? Multi-modal assessment of risk factors and predictors of pain chronification

Study Overview

• Status: Completed
• Conditions: Chronic Pain Due to Injury

Detailed Description

Background

The proposed study aims to explore why acute pain turns, in some patients, into chronic pain, and to develop tools for prediction of this transition. Based on the clinical and psychological assessment along with psychophysical and neurophysiological assessment of pain perception, with the analysis of connectivity between several brain centers relevant for pain processing, together with pain genetics, we expect to develop a tool, that will predict, for the individual patient with acute pain inflicted by a whiplash injury, what are the chances for him/her to go into chronic pain situation. Further, by knowing the dysfunctions of pain processing that a patient has, it will be possible to offer the treatment of highest chances to succeed.

Our specific aims are to evaluate, in the setup of acute whiplash injury, the risk of transition to chronic pain based on each of the following testing domains: (i) Psychophysical and neurophysiological data describing facilitatory and inhibitory modulation capacity of the patient. (ii) Psychological data describing patient's behavior such as catastrophizing, fear of pain, post-traumatic stress and depressed mood. (iii) Structural and functional neuro-imaging data describing brain anatomy and function, where we assess resting state MRI activity, grey matter properties using T1 weighted imaging, and white matter properties using diffusion tensor imaging. (iv) Genetic data describing the genetic epidemiology of every patient for the examination of genetic variants associated with transition to chronic pain, and (v) individual case data related to age, gender, education, socioeconomic parameters and personal medical history, as well as features of the specific injury. Overall, we aim to construct a composite scoring system, based on the most relevant of the above mentioned parameters, yielding the highest relative predictive value in identifying acute pain patients who have higher risk for chronification.

Subjects One hundred and twenty healthy subjects (range 20-79; 20 subjects per age decade, 10 M and 10 F) will participate in the first phase of the study aimed to collect normative data from healthy population.

Seven hundred and fifty acute whiplash-injury based mild traumatic brain injuries (TBI) will participate in this study.

Study design Phase I - Normative data collection for the inhibitory and excitatory pain modulation responses, a study on healthy subjects

Phase II - Multi-modal assessment of acute mild TBI whiplash patients and follow-up

1. Initial experimental assessment, will consist, in most cases, of two sessions, one during the ER visit, and the next within 72 hrs of injury, pending on team and device availability, such that all tests will be completed, as follows:

   1. Physical examination with a full neurological exam, and assessment of neck movement.
   2. Psychophysical pain measurements:

   i. Pain thresholds. ii. Suprathreshold pain magnitude estimation; iii. Mechanical temporal summation (TS) and electrical TS iv. Conditioned pain modulation (CPM) - as described for the phase I protocol. It is noted that similar protocols of pain measurement are commonly performed in many labs worldwide in many acute and chronic pain setups, and are considered safe, with no damaging effect on the disease state.

   c. Psychological examination via filling questionnaires for evaluation the following variables: i. Pain Catastrophizing ii. Depression iii. Post-traumatic Diagnostic Scale (PDS) iv. Fear of pain v. The perceived stress of the subjects is assessed by the validated Hebrew version Cohen's Perceived Stress Scale (PSS).

   vi. Five factor model (FFM)

   d.Blood collection for genetics. Whole blood sample (10cc) will be collected from each subject and placed in Ethylenediaminetetraacetic acid (EDTA)-coated tubes. Genomic DNA will be isolated using DNA Extraction Kit . Quality and quantity of the DNA sample will be measured using a NanoDrop Machine.

   e. Magnetic resonance imaging (MRI)/Functional MRI (fMRI) examination in a 3T scanner.

   f. Neurophysiological assessment of pain modulation with 64-channel EEG recording (Brain Products GmbH, Munich, Germany) of CPM and TS.

   i.Neurophysiological assessment of CPM ii.Neurophysiological assessment of TS will be based on electrical evoked potentials obtained with a constant current stimulator

2. Follow up Patients will self-report their pain levels and use of analgesics once in two weeks.

At 6 and 12 month visits patients will be invited to repeat the psychophysical and neurophysiological pain assessments and psychological questionnaires. Selected patients will undergo a second MRI assessment.

• Study Type: Observational
• Enrollment (Actual): 399

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel, 31096
    • Rambam Health Care Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

750 Subjects with acute post whiplash injury pain. and 120 healthy subjects .

Description

Inclusion criteria:

Diagnosis of whiplash injured in road accident up to 72h before ER arrival; Glasgow coma scale 13-15 and no traumatic brain findings in computed tomography (CT); no, or shorter than 30 minutes loss of consciousness in the accident. Age 18-70, both males and females.

Exclusion criteria:

Other major bodily injuries at present accident; intracranial hemorrhage or skull fracture in present accident, prior chronic head/neck pain that requires treatment on regular basis; neurological disease that might affect performance of the tests or their interpretation such as neurodegenerative diseases; head and neck injury in past year.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
120 healthy subjects; One hundred and twenty healthy subjects (range 20-79; 20 subjects per age decade, 10 M and 10 F) will participate in the first phase of the study aimed to collect normative data from healthy population. Study design Phase I - Normative data collection for the inhibitory and excitatory pain modulation responses, a study on healthy subjects (no blood tests)
750 subjects with acute whiplash-injury; Seven hundred and fifty acute whiplash-injury based mild TBI will participate in this study. Phase II - Multi-modal assessment of acute mild TBI whiplash patients and follow-up

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chronic pain	acute post whiplash injury pain transform into chronic pain	12 months

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus
• Collaborators: Technion, Israel Institute of Technology; Congressionally Directed Medical Research Programs
• Investigators: Principal Investigator: David Yarnitsky, Head of Neurology department at Rambam

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): September 15, 2021

Study Registration Dates

• First Submitted: September 24, 2015
• First Submitted That Met QC Criteria: September 24, 2015
• First Posted (Estimated): September 25, 2015

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Chronic Pain; TBI; Whiplash Injury Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Neck Injuries; Chronic Pain; Wounds and Injuries; Whiplash Injuries
• Other Study ID Numbers: 601-14-RMB Whiplash_CTIL; 597-14-RMB Gene_Whiplash_CTIL (Other Identifier: Rambam Genetic sub study)