Impact of Peripheral Afferent Input on Central Neuropathic Pain

The overarching aim of this study is to investigate the contribution of peripheral afferent input to spontaneous and evoked central neuropathic pain after a spinal cord lesion or disease.

Study Overview

• Status: Not yet recruiting
• Conditions: Spinal Cord Diseases; Spinal Cord Injuries; Syringomyelia
• Intervention / Treatment: Diagnostic test: Lidocaine (10 mg/ml); Diagnostic test: Isotonic saline

Detailed Description

A key question that has been subject to longstanding debates in the field relates to the sites and mechanisms within the peripheral or central nervous system that potentially perpetuate chronic spontaneous and evoked central neuropathic pain. The investigators hypothesize that spontaneous central neuropathic pain depends on continuous, "physiological" somatosensory input from the painful body region in the periphery. Thus, spontaneous central neuropathic pain results from pathological gain control in central somatosensory networks with decreased activation thresholds for thermo- and mechanosensitive peripheral afferents.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Nanna B. Finnerup, Professor; Phone Number: 0045 784 63380; Email: finnerup@clin.au.dk
• Study Contact Backup: Name: Jan Rosner, MD; Phone Number: 0041 79 952 4551; Email: jan.rosner@balgrist.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Definite central neuropathic pain according to current diagnostic algorithms involving at least both feet or both hands bilaterally and symmetrically with regard to the expected neuroanatomical distribution of the nerve block.
• Patients with spinal cord injury. For patients with pain in both legs, the injury has to be incomplete. For patients with pain in both arms, the injury can be complete or incomplete. The pain in the area that will be investigated (region of interest) has to be in an area with at least some preservation of sensation
• An intensity of spontaneous pain of ≥4 NRS [0-10] in the region of interest during the screening visit and at the day of the intervention.
• Participant is able and willing to give informed consent.
• For female subjects of childbearing potential: A negative pregnancy test and either use of highly effective contraception or sexual abstinence

Exclusion Criteria:

• Conus/cauda involvement or evidence of peripheral neuropathic pain due to documented peripheral lesion.
• Other known neurological and psychiatric conditions
• History or symptoms of significant diseases that may confound the measurements or represent contra-indications for the intervention (e.g., neuropathy following cancer or metabolic diseases such as diabetes mellitus, liver diseases, and kidney diseases.
• Cardiovascular diseases that preclude the anaesthetic intervention (e.g., arrythmias).
• Concomitant nociceptive pain within the innervation territory of the planned nerve block.
• Unable to understand and speak Danish
• Changes in pain medication within the last 4 weeks prior to the intervention.
• Treatment with warfarin or other blood thinning medications, that contraindicates regional anesthesia if the treating physician cannot recommend that such treatments are paused for at least 7 days before the study day
• Infection or skin disease in planned injection area
• Allergy for local anesthetics
• Pregnancy or lactation.
• Alcohol or drug abuse
• Pain intensity below 4 in the region of interest at the baseline measurement before the nerve block

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine; Nerve block	Diagnostic test: Lidocaine (10 mg/ml); Lidocaine (10 mg/ml) will be injected according to established protocols using ultrasound guidance and an aseptic technique by an experienced anesthesiologist.
Placebo Comparator: Isotonic saline; Nerve block	Diagnostic test: Isotonic saline; Isotonic saline will be injected according to established protocols using ultrasound guidance and an aseptic technique by an experienced anesthesiologist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indication of most pain relief	Limb with most pain relief on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] 40 minutes after nerve block	40 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain	Intensity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] of spontaneous pain in the pre-specified region covered by the block 40, 60 and 90 min after the nerve block compared to baseline	90 minutes
Pain relief 45 min after the nerve block	Pain relief 45 min after the nerve block using a 6-point verbal scale ranging from worse pain to no, little, moderate, good and complete pain relief (-1 to 4)	45 minutes
Pain extent [% of body surface on standardized pain drawings] 50 minutes after the nerve block	Pain extent will be mapped on standardized pain drawings 50 minutes after the nerve block compared to baseline	50 minutes
Pain descriptors 50 minutes after the nerve block	Pain descriptors (burning, squeezing, pins and needles, tingling, stabbing, electrical shocks) are captured 50 minutes after the nerve block compared to baseline	50 minutes
Area [% of pain extent] of hypersensitivity to thermal and nociceptive stimuli	Area of hypersensitivity [% of pain extent] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline	95 minutes
Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to thermal and nociceptive stimuli	Intensity of hypersensitivity on Numerical Rating Scale (NRS) [0-10, 0=no pain 10=worst pain imaginable] to warm (40°C) and cold (20°C) thermo rollers (Somedic AB, Hörby, Sweden), pinprick (Semmes-Weinstein monofilament no 5.88 (bending force 75.9 g/745 mN)), and brush (SENSELab Brush-05; Somedic AB, Hörby, Sweden), if any, 55 and 95 min after nerve block compared to baseline	95 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma lidocaine concentrations	Plasma lidocaine concentrations approx. 40 min after the block.	40 minutes

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Principal Investigator: Jan Rosner, MD, Danish Pain Research Center, Department of Clinical Medicine, Aarhus University

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 14, 2022
• First Submitted That Met QC Criteria: December 2, 2022
• First Posted (Estimate): December 12, 2022

Study Record Updates

• Last Update Posted (Estimate): December 12, 2022
• Last Update Submitted That Met QC Criteria: December 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: neuropathic pain; spinal cord injury; central pain; peripheral afferent input
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Wounds and Injuries; Neuromuscular Diseases; Peripheral Nervous System Diseases; Trauma, Nervous System; Neuralgia; Spinal Cord Diseases; Spinal Cord Injuries; Syringomyelia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Membrane Transport Modulators; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Lidocaine
• Other Study ID Numbers: 39451

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