The Nociceptive Flexion Reflex as a Diagnostic Tool of Central Sensitization

Recruiting

• Conditions: Central Sensitisation; Low Back Pain; Fibromyalgia; Neck Pain; Whiplash

• Registration Number: NCT05321550
• Lead Sponsor: University Ghent

Brief Summary

This experimental study will investigate whether the decreased NFR threshold and increased NFR temporal summation, which are frequently observed in chronic pain patients, are only symptomatic manifestations that occur in the involved limb and indicate peripheral sensitization or generalized manifestations that are also present in the non-involved limbs and thus indicate central sensitization. To gain an idea of the presence of central sensitization, this study will also investigate whether there are increased perception and decreased pain thresholds in response to electrical, thermal, and mechanical stimulation, as well as whether there is a decreased conditioned pain modulation. To investigate this, it is essential to examine different pain populations and locations, in particular, acute pain versus chronic pain populations to compare peripheral versus central sensitization, respectively. Recently, our research group has shown that patients with a traumatic origin of chronic neck pain (chronic whiplash-associated disorders) show central sensitization in contrast to patients with a non-traumatic origin (chronic idiopathic neck pain) who demonstrate only indications for peripheral sensitization. Therefore, this study will also distinguish between complaints of traumatic and non-traumatic origin.

The measurements will be performed at different locations, namely the lower and upper limbs. To determine whether the differences depend on the measurement location (= location where experimental nociceptive stimulation is administered) and symptom location (= location of clinical nociceptive stimulation), different patient populations will be compared with each other, as well as with a healthy control population. In acute and chronic whiplash patients and patients with acute and chronic idiopathic neck pain complaints, the complaints are primarily localized in the upper limb. It is hypothesized that in chronic neck pain patients (both whiplash and idiopathic neck pain patients) abnormal values are found in both the upper and lower limbs compared to the healthy controls due to central sensitization. In acute neck pain patients (both whiplash and idiopathic neck pain) only abnormal values in the arm are expected and not in the leg as a result of peripheral sensitization. It is hypothesized that patients with neck pain of traumatic origin will show a stronger sensitization than those with neck pain of non-traumatic origin. In acute and chronic low back pain patients, the complaints are primarily localized in the lower body quadrant. As a result of central sensitization in the chronic low back pain patients, abnormal values are expected in both the upper and lower limbs, while only abnormal values in the leg are expected as a result of peripheral sensitization in the acute low back pain patients. Finally, this study will investigate whether chronic low back and neck pain patients show a similar pattern of central sensitization as fibromyalgia patients, a population with generalized complaints that are primarily attributed to central sensitization.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-22
• Study First Submitted QC: 2022-04-01
• Study First Posted: 2022-04-11
• Study Start: 2022-04-21
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-04
• Last Update Posted: 2024-01-05
• Primary Completion: 2024-10
• Study Completion: 2024-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

Inclusion Criteria

Not provided

Exclusion Criteria

• history of severe respiratory (e.g. cystic fibrosis), orthopedic (e.g. whiplash trauma), neurological (e.g. cerebrovascular incident), cardiovascular (e.g. severe hypertension), or endocrinological (e.g. diabetes) disorders
• recent psychological trauma (e.g. post-traumatic stress disorder)
• history of spinal surgery (e.g. lumbar discectomy), spinal trauma (e.g. vertebral fracture), or severe spinal deformities (e.g. spondylolisthesis)
• BMI ≥35 (due to potential difficulties in obtaining an NFR in severely overweight individuals)
• having pacemakers and defibrillators (absolute exclusion criteria for electrical stimulus stimulation, i.e. TENS)
• pregnancy, lactation, or within 1 year postpartum

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Quantitative sensory testing (QST) - electrical pain threshold	Baseline	Determination of sensory pain threshold in response to electrical stimuli which are delivered transcutaneously over the n. suralis and n. medianus, recorded in mA.
Quantitative sensory testing (QST) - spinal hyperexcitability	Baseline	Determination of spinal hyperexcitability using the nociceptive flexion reflex (NFR; sensitization of spinal cord neurons), recorded in mA
Quantitative sensory testing (QST) - discrimination between thermal stimuli	Baseline	Determination of the number of paradoxical heat sensations in response to alternating cold and warm stimuli delivered to the skin using a thermode.
Quantitative sensory testing (QST) - mechanical pain threshold	Baseline	Determination of mechanical pain threshold, assessed using pinprick stimulators, recorded in mN
Quantitative sensory testing (QST) - temporal summation of spinal hyperexcitability	Baseline	Determination of temporal summation of the nociceptive flexion reflex (NFR; sensitization of spinal cord neurons), recorded using a numeric pain rating scale (range 0 - 100)
Quantitative sensory testing (QST) - thermal detection threshold	Baseline	Determination of sensory detection thresholds in response to thermal stimuli which are delivered to the skin using a thermode, recorded in °C: * cold detection threshold; * warmth detection threshold
Quantitative sensory testing (QST) - thermal pain threshold	Baseline	Determination of sensory pain thresholds in response to thermal stimuli which are delivered to the skin using a thermode, recorded in °C: * cold pain threshold; * heat pain threshold
Quantitative sensory testing (QST) - tactile detection threshold	Baseline	Determination of tactile detection threshold, assessed using Von Frey monofilaments, recorded in mN
Quantitative sensory testing (QST) - sensitivity to pressure stimuli	Baseline	Determination of pressure pain threshold, assessed using pressure algometry, recorded in kg
Quantitative sensory testing (QST) - temporal summation of electrical stimuli	Baseline	Determination of temporal summation in response to electrical stimuli delivered transcutaneously over the skin of the n. suralis and n. medianus.; The numerical pain rating in response to these stimuli (range 0 - 100) will be recorded.
Quantitative sensory testing - conditioned pain modulation	Baseline	Determination of condition pain modulation (aka. pain inhibits pain) by means of a heterotopic noxious counterstimulation paradigm. Test stimuli comprise of pressure pain threshold assessments and application of a heat stimulus (using a thermode) corresponding to a temperature eliciting a visual analog scale rating of 5/10. Test stimuli will be applied before, during and after the conditioning stimulus which is the immersion of the hand in a hot circulating water bath of 45.5°C.
Quantitative sensory testing (QST) - electrical detection threshold	Baseline	Determination of sensory detection thresholds in response to electrical stimuli which are delivered transcutaneously over the n. suralis and n. medianus, recorded in mA.

Secondary Outcome Measures

Name	Time	Method
Tampa scale for kinesiophobia	Baseline	Self-report measure assessing fear of movement
Central sensitization inventory	Baseline	Self-report measure of signs and symptoms associated with central sensitization
Pain catastrophizing scale	Baseline	Self-report measure of pain perceptions and cognitions
International physical activity questionnaire	Baseline	Self-report measure of physical activity in preceeding 7 days
Patient-reported outcomes measurement information system - depression	Baseline	Self-report measure of health-related domains relating to depression
Pain vigilance and awareness questionnaire	Baseline	Self-report measure assessing preoccupation with and attention to pain
Patient-reported outcomes measurement information system - fatigue	Baseline	Self-report measure of health-related domains relating to fatigue and sleep disruption
Patient-reported outcomes measurement information system - pain interference	Baseline	Self-report measure of health-related domains relating to pain interference
Injustice Experience Questionnaire	Baseline	Self-report measure of perceived injustice
Douleur Neuropathique 4 Questionnaire	Baseline	Clinician administered questionnaire for evaluation of signs and symptoms associated with neuropathic pain
Patient-reported outcomes measurement information system - physical functioning	Baseline	Self-report measure of health-related domains relating to physical functioning
Patient-reported outcomes measurement information system - anxiety	Baseline	Self-report measure of health-related domains relating to anxiety
Patient-reported outcomes measurement information system - participation	Baseline	Self-report measure of health-related domains relating to participation in social activities
Pain Disability Index	Baseline	Self-report measure of pain-related disability

Trial Locations

Locations (1)

Ghent University; 🇧🇪 Ghent, Belgium