Neuropathy, Nociceptive Pain, Pain, Neuropathic, Spinal Cord Injuries
Conditions
Brief summary
The development of neuropathic pain is one of the most debilitating sequels after a spinal cord injury (SCI). The overall aim of this study is to investigate potential underlying pathophysiological mechanisms of neuropathic pain after SCI. The functionality of the nociceptive pathway in humans as well as its plastic changes following SCI will be inferred with sophisticated sensory and pain phenotyping using quantitative sensory testing (i.e., psychophysical measures), objective neurophysiological measures of pain processing and the recording of pain-related autonomic responses (i.e., galvanic skin response, cardiovascular measures and pupil dilation). In addition, the interplay between the somatosensory and autonomic nervous system and its association with the development and maintenance of neuropathic pain after SCI will be investigated.
Interventions
DIAGNOSTIC_TESTNeurophysiology
Pain-related evoked potentials and nerve conduction studies
DIAGNOSTIC_TESTCardiovascular test
Blood pressure control, orthostatic intolerance test, baro-reflex sensitivity, heart-rate variability
DIAGNOSTIC_TESTExperimental pain paradigms
Temporal summation of pain, conditioned pain modulation, offset analgesia
DIAGNOSTIC_TESTQuantitative sensory testing
Thermal and mechanical sensory testing
DIAGNOSTIC_TESTClinical pain phenotype
Pain drawings, plus and minus signs of pain
DIAGNOSTIC_TESTPupillometry
Pupil size changes after phasic and tonic sensory stimulation
Sponsors
University of Zurich
Swiss National Science Foundation
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Spinal injury cohort - general inclusion criteria: * Aged between 18-80 years * Traumatic and non-traumatic etiology * Para- and tetraplegic SCI * Complete and incomplete SCI * SCI with and without neuropathic pain * Additional inclusion criteria for longitudinal study: * SCI since less than one month * Additional inclusion criteria for cross-sectional study: * SCI since more than one year * Control cohorts with peripheral neuropathy: * General inclusion criteria: * Aged between 18-80 years * Neurological disorder affecting the peripheral nervous system (i.e., peripheral neuropathy) * Peripheral neuropathy with or without neuropathic pain * Additional inclusion criteria for longitudinal study: * Peripheral neuropathy since less than one month * Additional inclusion criteria for cross-sectional study: * Peripheral neuropathy since more than one year * Control cohorts without neuropathy / healthy volunteers * General inclusion criteria: * Aged between 18-80 years * No medical condition affecting the peripheral and/or central nervous system (e.g., pain, systemic disease, psychological disorder)
Exclusion criteria
* Inability to follow study instructions * Pregnancy * Medically manifested psychological disorder * Medical condition affecting the peripheral and/or central nervous system other than the desired experimental condition (e.g., additional peripheral neuropathy in the SCI cohort)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients with peripheral neuropathy: clinical pain phenotype including the spatial pain extent and pain intensity | Cross-sectional: once in a chronic stage (1 year post-injury) | Pain drawings, plus and minus signs of pain |
| Spinal cord injury patients: clinical pain phenotype including the spatial pain extent and pain intensity | Longitudinal: change from 1 month up to 12 months | Pain drawings, plus and minus signs of pain |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Spinal cord injury patients / patients with peripheral neuropathy / healthy controls: pupillometry | Cross-sectional: once in a chronic stage (1 year post-injury) | Change in pupil size in mm after sensory input (noxious, non-noxious) |
| Spinal cord injury patients / patients with peripheral neuropathy / healthy controls: offset analgesia (psychophysical) | Cross-sectional: once in a chronic stage (1 year post-injury) | Change in pain ratings during tonic heat stimulation (offet analgesia paradigm) in numeric rating scale (NRS, scale titel: offset analgesia, 0-100, higher score means better analgesia) |
| Spinal cord injury patients / patients with peripheral neuropathy / healthy controls: offset analgesia (pupillometry) | Cross-sectional, once in a chronic stage (1 year post-injury) | Change in pupil size in mm during tonic heat application (offseat analgesia paradigm) |
| Spinal cord injury patients / healthy controls: somato-sensory evoked potentials | Longitudinal: change from 1 month up to 12 months | Amplitude in uV |
| Spinal cord injury patients / healthy controls: contact-heat evoked potentials | Longitudinal: change from 1 month up to 12 months | Amplitude in uV |
| Spinal cord injury patients / healthy controls: N13 spinal potential | Longitudinal: change from 1 month up to 12 months | Amplitude in uV |
| Spinal cord injury patients / healthy controls: motor neurographies | Longitudinal: change from 1 month up to 12 months | Amplitude in mV |
| Spinal cord injury patients / healthy controls: sensory neurography | Longitudinal: change from 1 month up to 12 months | Amplitude in mV |
| Spinal cord injury patients / healthy controls: resting blood pressure | Cross-sectional: once in a chronic stage (1 year post-injury) | Systolic, diastolic and mean arterial pressure all in mmHg variability |
| Patients with peripheral neuropathy / healthy controls: changes in blood pressure after a cold pressure test | Cross-sectional: once in a chronic stage (1 year post-injury) | Delta mmHg |
| Patients with peripheral neuropathy / healthy controls: changes in blood pressure after a Valsalva maneuvre | Cross-sectional: once in a chronic stage (1 year post-injury) | Delta mmHg |
| Patients with peripheral neuropathy / healthy controls: changes in blood pressure after a sit-up test | Cross-sectional: once in a chronic stage (1 year post-injury) | Delta mmHg |
| Patients with peripheral neuropathy / healthy controls: baro-reflex sensitivity | Cross-sectional: once in a chronic stage (1 year post-injury) | ms/mmHg |
| Patients with peripheral neuropathy / healthy controls: heart rate variability | Cross-sectional: once in a chronic stage (1 year post-injury) | RMSSD (root mean square of successive differences), high frequency/low frequency ratio |
| Spinal cord injury patients / healthy controls: temporal summation of pain after repetitive application of 12 pinprick stimuli | Longitudinal: change from 1 month up to 12 months | Change in numeric rating scale of pain from the first three to the last three pinprick stimuli |
| Spinal cord injury patients / healthy controls: conditioned pain modulation | Longitudinal: change from 1 month up to 12 months | Changes in pressure pain threshold (measured by an algometer in delta kg) before and during a cold water bath |
| Patients with peripheral neuropathy / healthy controls: temporal summation of pain after repetitive application of 12 pinprick stimuli | Longitudinal: change from 1 month up to 12 months | Change in numeric rating scale of pain from the first three to the last three pinprick stimuli |
| Patients with peripheral neuropathy / healthy controls: conditioned pain modulation | Longitudinal: change from 1 month up to 12 months | Changes in pressure pain threshold (measured by an algometer in delta kg) before and during a cold water bath |
| Spinal cord injury patients / healthy controls: thermal sensory testing tested with a thermode | Longitudinal: change from 1 month up to 12 months | Warm detection threshold (°C), cold detection threshold (°C), heat pain threshold (°C), cold pain threshold (°C) |
| Patients with peripheral neuropathy / healthy controls: thermal sensory testing tested with a thermode | Longitudinal: change from 1 month up to 12 months | Warm detection threshold (°C), cold detection threshold (°C), heat pain threshold (°C), cold pain threshold (°C) |
| Spinal cord injury patients / healthy controls: mechanical sensory testing tested with von Frey monofilaments/pinpricks | Longitudinal: change from 1 month up to 12 months | Mechanical detection threshold (mN) |
| Patients with peripheral neuropathy / healthy controls: mechanical sensory testing tested with von Frey monofilaments/pinpricks | Longitudinal: change from 1 month up to 12 months | Mechanical detection threshold (mN) |
Countries
Switzerland
Contacts
CONTACTMichèle Hubli, PD Dr.
PRINCIPAL_INVESTIGATORPatrick Freund, Prof. Dr. Dr.
University of Zurich
Outcome results
None listed