Identifying Pain Generators and Potentiators of Residual Complaints Following Lumbar Discectomy

Study Overview
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Brief Summary
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Lumbar discectomy (i.e. surgically removing a hernia) is frequently performed in Belgium to treat lumbar radiculopathy. Every year >12,000 interventions are performed with variable long-term results. The treatment success of this procedure varies and up to 41% of the patients report post-operative persistent pain complaints, and consequently suffer from failed back surgery syndrome (FBSS). Chronic complaints in FBSS following lumbar discectomy are usually treated with symptomatic interventions (including painkillers, neuromodulation, etc), rather than from a biopsychosocial perspective. In order to develop a focused and effective treatment strategy, it is crucial to first gain insight into how persons with persistent complaints after lumbar discectomy differ from those without persistent symptoms. Different known contributing factors entail type of surgery, muscle and psychosocial impairments. Although in scientific and clinical literature it is assumed that dysfunctional pain processing also plays an important mechanistic role in FBSS, there is a lack of research to support this. However, this knowledge is crucial to depict the full mechanistic picture of pain generators and potentiators in FBSS. Therefore, we will examine whether residual complaints persisting following lumbar discectomy can be accounted for by underlying dysfunctional pain processing and whether a clinical classification algorithm can be used to identify the predominant pain mechanism in these patients.

Official Title
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Identifying Pain Generators and Potentiators of Residual Complaints Following Lumbar Discectomy

Conditions
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Lumbar Radiculopathy, Central Sensitisation

Intervention / Treatment
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* Procedure: Lumbar discectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dutch speaking Body mass index below 35kg/m² Lumbar radiculopathy patients, classified as ASA I to II without any symptoms of spinal cord compression (i.e. bilateral leg pain), who are scheduled for a first-time, single-level, unilateral lumbar discectomy Healthy, pain-free controls (score 0 on a visual analogue scale from 0 to 100) Exclusion Criteria: Female participants will be excluded if pregnant, lactating or <1 year postnatal Having (a history) of severe medical disorders either respiratory (e.g. cystic fibrosis), orthopedic (e.g. whiplash trauma), neurologic (e.g. cerebrovascular incident), cardiovascular (e.g. severe hypertension), endocrinological (e.g. diabetes), psychiatric (e.g. post-traumatic stress disorder Having a history of spinal surgery (e.g. discectomy), spinal traumata (e.g. vertebral fracture) or severe spinal deformities (e.g. spondylolisthesis) Having a pacemaker or defibrillator Healthy controls will be excluded if having suffered low back pain in the preceding year of score 2 or higher on the visual analog scale and which limited their activities of daily living or for which they consulted a (para)medic.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lumbar radiculopathy<br>Lumbar radiculopathy patients (n=122), classified as ASA I to II without any symptoms of spinal cord compression (i.e. bilateral leg pain), who are scheduled for a first-time, single-level, unilateral lumbar discectomy. | Procedure: Lumbar discectomy<br>* surgically removing a hernia<br>|
| Healthy controls<br>Sex, age, and BMI-matched healthy, pain-free control subjects (n=122) will be recruited for study participation. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative sensory testing (QST) - electrical detection threshold | Determination of sensory detection thresholds in response to electrical stimuli which are delivered transcutaneously over the n. suralis and n. medianus, recorded in mA. | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - electrical pain threshold | Determination of sensory pain threshold in response to electrical stimuli which are delivered transcutaneously over the n. suralis and n. medianus, recorded in mA. | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - thermal detection threshold | 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 | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - thermal pain threshold | 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 | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - discrimination between thermal stimuli | Determination of the number of paradoxical heat sensations in response to alternating cold and warm stimuli delivered to the skin using a thermode. | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - tactile detection threshold | Determination of tactile detection threshold, assessed using Von Frey monofilaments, recorded in mN | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - mechanical pain threshold | Determination of mechanical pain threshold, assessed using pinprick stimulators, recorded in mN | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - sensitivity to pressure stimuli | Determination of pressure pain threshold, assessed using pressure algometry, recorded in kg | Change from baseline (T1) at 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - temporal summation of electrical stimuli | 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. | Change from baseline (T1) and 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - temporal summation of mechanical stimuli | Determination of temporal summation in response to mechanical stimuli delivered using a 256mN pinprick stimulator. The numerical pain rating in response to these stimuli (range 0 - 100) will be recorded. | Change from baseline (T1) and 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - spinal hyperexcitability | Determination of spinal hyperexcitability using the nociceptive flexion reflex (NFR; sensitization of spinal cord neurons), recorded in mA | Change from baseline (T1) and 3 months after surgery (T2) | 
| Quantitative sensory testing (QST) - temporal summation of spinal hyperexcitability | 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) | Change from baseline (T1) and 3 months after surgery (T2) | 
| Quantitative sensory testing - conditioned pain modulation | 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. | Change from baseline (T1) and 3 months after surgery (T2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Central sensitization inventory | Self-report measure of signs and symptoms associated with central sensitization | Baseline (T1) | 
| Central sensitization inventory | Self-report measure of signs and symptoms associated with central sensitization | 3 months after surgery (T2) | 
| Douleur Neuropathique 4 Questionnaire | Clinician administered questionnaire for evaluation of signs and symptoms associated with neuropathic pain | Baseline (T1) | 
| Douleur Neuropathique 4 Questionnaire | Clinician administered questionnaire for evaluation of signs and symptoms associated with neuropathic pain | 3 months after surgery (T2) | 
| Pain catastrophizing scale | Self-report measure of pain perceptions and cognitions | Baseline (T1) | 
| Pain catastrophizing scale | Self-report measure of pain perceptions and cognitions | 3 months after surgery (T2) | 
| Pain vigilance and awareness questionnaire | Self-report measure assessing preoccupation with and attention to pain | Baseline (T1) | 
| Pain vigilance and awareness questionnaire | Self-report measure assessing preoccupation with and attention to pain | 3 months after surgery (T2) | 
| Oswestry disability index | Self-report measure evaluating low back pain related disability | Baseline (T1) | 
| Oswestry disability index | Self-report measure evaluating low back pain related disability | 3 months after surgery (T2) | 
| Tampa scale for kinesiophobia | Self-report measure assessing fear of movement | Baseline (T1) | 
| Tampa scale for kinesiophobia | Self-report measure assessing fear of movement | 3 months after surgery (T2) | 
| International physical activity questionnaire | Self-report measure of physical activity in preceeding 7 days | Baseline (T1) | 
| International physical activity questionnaire | Self-report measure of physical activity in preceeding 7 days | 3 months after surgery (T2) | 
| Patient-reported outcomes measurement information system | Self-report measure of health-related domains including: physical functioning anxiety depression fatigue sleep disruption participation in social activities pain interference | Baseline (T1) | 
| Patient-reported outcomes measurement information system | Self-report measure of health-related domains including: physical functioning anxiety depression fatigue sleep disruption participation in social activities pain interference | 3 months after surgery (T2) | 
| Brief Illness Perception Questionnaire | Self-report measure evaluating illness perceptions | Baseline (T1) | 
| Brief Illness Perception Questionnaire | Self-report measure evaluating illness perceptions | 3 months after surgery (T2) | 
| Pain Coping Inventory | Self-report measure assessing pain coping strategies | Baseline (T1) | 
| Pain Coping Inventory | Self-report measure assessing pain coping strategies | 3 months after surgery (T2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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lumbar radiculopathy, discectomy, central sensitization