Changes in Radicular Pain and Pain Modulation

The Association Between Changes in Radicular Pain and Pain Modulation Among Patients With Lumbar Radiculopathy: A Pilot Study.

The objectives of this study are: 1)To investigate the difference in pain modulatory mechanisms using quantitative sensory testing (QST) between healthy controls and patients with radicular leg pain due to nerve root compression. 2) To investigate the association between changes in radiating leg pain and pain modulation among the patient group.

Study Overview

• Status: Completed
• Conditions: Back Pain; Back Pain With Radiation
• Intervention / Treatment: Diagnostic test: Pressure pain assessment using computer controlled cuff algometry; Diagnostic test: Temporal summation (TS); Diagnostic test: Conditioned pain modulation (CPM); Diagnostic test: Low back pain rating scale (LBPRS-pain); Diagnostic test: Oswestry Disability Index

Detailed Description

Few studies have investigated pain modulatory mechanisms using QST in patients with lumbar radiculopathy due to nerve root compression. Knowledge about the association between changes in the experience of pain and changes measures of pain modulation is to our knowledge limited. The results could potentially contribute to knowledge about mechanisms involved in lumbar radiculopathy and facilitate future studies. The hypotheses of the study are: 1) Measures of pain modulation will be less efficient among patients with lumbar radiculopathy showing reduced pain inhibition and facilitated temporal summation compared to healthy controls. 2) Improvements in pain modulation will be associated with improvements in clinical pain outcomes

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Middelfart, Denmark, 5500
    • Spine Centre of Southern Denmark

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Patient group

• Radiating leg pain due to nerve root compression verified by MRI
• Clinical findings in accordance with MRI findings
• Average leg pain ≥ 3/10 on a numeric pain rating scale Controls
• No current or previous history of ongoing musculoskeletal pain

Exclusion Criteria:

Applies for both groups.

• Other specific medical conditions e.g. rheumatologic disease, diabetes or vascular diseases.
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiculopathy due to nerve root compression; Participants with radicular leg pain due to lumbar disc herniation or to foraminal- or recess stenosis. Baseline assessments of pain intensities are performed through questionnaires prior to protocol. Data regarding initial pain, function, age, gender, pain-duration, weight and height is retrieved from the clinical registry SpineData. Pain sensitivity, temporal summation and conditioned pain modulation are assessed at the first visit in the treatment program. The protocol is repeated at the last visit in the treatment program.	Diagnostic test: Pressure pain assessment using computer controlled cuff algometry; Pressure pain sensitivity is assessed. The pressure is gradually increased and pain is rated by the participant on an electronic visual analogue pain rating scale (VAS) which is connected to the equipment. The assessment is performed on the lower leg and the upper arm. The pain free leg and the left upper arm is used in the patient group. The leg used in the control group will be chosen in a balanced manner meaning that half will receive pressure on the left leg and the other half on the right leg. The pain detection threshold (PDT), pain pressure tolerance threshold (PPT) and pressure pain intensity perceived as 6 on the VAS (VAS6) at the leg site is registered. The PDT and PPT on the arm site is registered.; Other Names: Assessment of pain sensitivity; Diagnostic test: Temporal summation (TS); 10 repeated inflations on the lower leg with a 1 sec interval. The pressure used at each pressure is equivalent the PPT measured at baseline. Each inflation is rated on the VAS. TS is registered as the increase pain intensity.; Other Names: Repeated pressure pain; Diagnostic test: Conditioned pain modulation (CPM); The cuff on the upper arm is inflated until 70% of the PPT is reached. While the pressure on the arm is kept constant the cuff on the leg is inflated. PDT, PPT and VAS6 pressure at the leg site is registered during the tonic stimulation (pressure on the left arm). The procedure on the leg is repeated within 30 seconds after the pressure is released on the arm site.; Other Names: Pain inhibition; Diagnostic test: Low back pain rating scale (LBPRS-pain); A questionnaire measuring the intensities of low back pain and leg pain currently, on average the last two weeks and the worst pain within the same period.; Other Names: Pain intensity; Diagnostic test: Oswestry Disability Index; A questionnaire measuring the disability in relation to low back pain and leg pain.; Other Names: Disability
Experimental: Healthy controls; Healthy controls Healthy age and gender-matched controls. Gender, weight and height are registered on questionnaires prior to protocol. Pain sensitivity, temporal summation and conditioned pain modulation are assessed at the first visit. The tests are repeated at the next visit. The interval between the two sessions will be determined by the averaged interval between tests in the patient group.	Diagnostic test: Pressure pain assessment using computer controlled cuff algometry; Pressure pain sensitivity is assessed. The pressure is gradually increased and pain is rated by the participant on an electronic visual analogue pain rating scale (VAS) which is connected to the equipment. The assessment is performed on the lower leg and the upper arm. The pain free leg and the left upper arm is used in the patient group. The leg used in the control group will be chosen in a balanced manner meaning that half will receive pressure on the left leg and the other half on the right leg. The pain detection threshold (PDT), pain pressure tolerance threshold (PPT) and pressure pain intensity perceived as 6 on the VAS (VAS6) at the leg site is registered. The PDT and PPT on the arm site is registered.; Other Names: Assessment of pain sensitivity; Diagnostic test: Temporal summation (TS); 10 repeated inflations on the lower leg with a 1 sec interval. The pressure used at each pressure is equivalent the PPT measured at baseline. Each inflation is rated on the VAS. TS is registered as the increase pain intensity.; Other Names: Repeated pressure pain; Diagnostic test: Conditioned pain modulation (CPM); The cuff on the upper arm is inflated until 70% of the PPT is reached. While the pressure on the arm is kept constant the cuff on the leg is inflated. PDT, PPT and VAS6 pressure at the leg site is registered during the tonic stimulation (pressure on the left arm). The procedure on the leg is repeated within 30 seconds after the pressure is released on the arm site.; Other Names: Pain inhibition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cuff sensitivity, measured with computer-controlled cuff algometry	Change in pain sensitivity between baseline and follow-up. Cuff is placed around the lower leg and on the upper arm and gradually inflated (1kPa/sec) on each location separately. In patients, the cuff is placed on the non-painful leg and left upper arm, in healthy controls, half of the participants the cuff is placed on the left leg and half on the right leg, while the other cuff is placed on the left upper arm. First, the pressure needed to evoke an onset of pain (pain detection threshold, PDT), the pressure at pain intensity VAS 6 (Measured on an electronic visual analogue scale: 0=No pain, 10=worst pain imaginable pain) and pain tolerance threshold (PTT) is assessed on the lower leg. Secondly, the PDT and the PTT is assessed on the left upper arm.	At baseline and at discharge from treatment throughout study completion, an average of 6 months. The timeframe between the baseline test and follow up test for controls will be matched the patient group.
Temporal summation of pain (increase in pain during repeated pain stimuli at same intensity) measured with computer-controlled cuff algometry	Change in pain intensity between baseline and follow-up. Cuff is placed on the lower leg. In patients the non-painful leg is used, in healthy controls, half of the participants will be tested on the left leg and half on the right leg. 10 painful stimuli are performed with a one-second interval in between. After each stimulus, the participant rates the pain intensities using an electronic VAS ( 0=No pain, 10=worst pain imaginable pain). The increase in pain intensity is defined as temporal summation.	At baseline and at discharge from treatment throughout study completion, an average of 6 months. The timeframe between the baseline test and follow up test for controls will be matched the patient group.
Conditioned pain modulation (change in pain sensitivity during a competing pain stimulus) measured with computer-controlled cuff algometry	Change in pain intensity between baseline and follow-up. Cuff is placed on the lower leg. In patients the non-painful leg is used, in healthy controls, half of the participants will be tested on the left leg and half on the right leg. 10 painful stimuli are performed with a one-second interval in between. After each stimulus, the participant rates the pain intensities using an electronic VAS ( 0=No pain, 10=worst pain imaginable pain). The increase in pain intensity is defined as temporal summation.	At baseline and at discharge from treatment throughout study completion, an average of 6 months. The timeframe between the baseline test and follow up test for controls will be matched the patient group.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leg pain (measured on the low back pain rating scale)	Change in pain between post-treatment and pre-treatment. The average pain during the last two weeks, the worst pain experienced during the same period and current pain is rated by the patient. Range 0-30. 0=no pain, 30= Worst pain imaginable.	At baseline and at discharge from treatment throughout study completion, an average of 6 months.
Back pain and leg pain (measured on the low back pain rating scale)	Change in pain between post-treatment and pre-treatment. Low back pain rating scale (LBPRS - pain): Two questionnaires with three numeric 11-point box scales (0-10) regarding low back pain and leg pain respectively. The average pain during the last two weeks, the worst pain experienced during the same period and current pain is rated by the patient. Range 0-60. 0=no pain, 60= Worst pain imaginable.	At baseline and at discharge from treatment throughout study completion, an average of 6 months.
Disability (Measured on the Oswestry Disability index)	Change in disability between post-treatment and pretreatment. Range 0-100, 0= No disability, 100 maximum disability possible.	At baseline and at discharge from treatment throughout study completion, an average of 6 months.

Collaborators and Investigators

• Sponsor: Spine Centre of Southern Denmark
• Investigators: Principal Investigator: Berit Schiøtzz-Christensen, Professor, Research department of Spine Center of Southern Denmark

Publications and helpful links

General Publications

• Vaegter HB, Palsson TS, Graven-Nielsen T. Facilitated Pronociceptive Pain Mechanisms in Radiating Back Pain Compared With Localized Back Pain. J Pain. 2017 Aug;18(8):973-983. doi: 10.1016/j.jpain.2017.03.002. Epub 2017 Mar 24.
• Mehta V, Snidvongs S, Ghai B, Langford R, Wodehouse T. Characterization of peripheral and central sensitization after dorsal root ganglion intervention in patients with unilateral lumbosacral radicular pain: a prospective pilot study. Br J Anaesth. 2017 Jun 1;118(6):924-931. doi: 10.1093/bja/aex089.
• Yarnitsky D. Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain. 2015 Apr;156 Suppl 1:S24-S31. doi: 10.1097/01.j.pain.0000460343.46847.58.
• Graven-Nielsen T, Izumi M, Petersen KK, Arendt-Nielsen L. User-independent assessment of conditioning pain modulation by cuff pressure algometry. Eur J Pain. 2017 Mar;21(3):552-561. doi: 10.1002/ejp.958. Epub 2016 Nov 11.
• Graven-Nielsen T, Vaegter HB, Finocchietti S, Handberg G, Arendt-Nielsen L. Assessment of musculoskeletal pain sensitivity and temporal summation by cuff pressure algometry: a reliability study. Pain. 2015 Nov;156(11):2193-2202. doi: 10.1097/j.pain.0000000000000294.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): September 21, 2021

Study Registration Dates

• First Submitted: November 24, 2019
• First Submitted That Met QC Criteria: December 8, 2019
• First Posted (Actual): December 11, 2019

Study Record Updates

• Last Update Posted (Actual): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 6, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: low back pain; radiculopathy; conditioned pain modulation; temporal summation
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain
• Other Study ID Numbers: S-20190091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No