Impact of Peripheral Afferent Input on Central Neuropathic Pain

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Impact of Peripheral Afferent Input on Central Neuropathic Pain

Conditions
-----------------
Spinal Cord Injuries, Spinal Cord Diseases, Syringomyelia

Intervention / Treatment
-----------------
* Diagnostic Test: Lidocaine (10 mg/ml)
* Diagnostic Test: Isotonic saline


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
central pain, peripheral afferent input, neuropathic pain, spinal cord injury