Neuromodulation in Lower Limb Amputees

Not Applicable

Terminated

Conditions: Hoffman's Reflex
Amputation
Phantom Limb Pain

Interventions: Device: Transcutaneous spinal cord stimulation

Registration Number: NCT04543786

Lead Sponsor: University of Pittsburgh

Brief Summary: The goal of this study is to investigate the role of transcutaneous spinal cord stimulation on spinal cord excitability in lower limb amputees. In this study, the investigators will quantify the spinal cord excitability determined by 1) reflexes and electromyography, and 2) phantom limb pain using self-reported pain assessments. The investigators will assess these measures of spinal excitability in lower limb amputees before and after transcutaneous spinal cord stimulation.

Detailed Description: The overall goal of this work is to investigate the changes in the spinal cord resulting from limb amputation. Limb amputation results in an extreme form of peripheral nerve injury. Damage to peripheral nerves, such as with neuropathy, crush injuries, nerve transection, or limb amputation often results in chronic pain, which may be associated with altered excitability of spinal sensorimotor pathways. These spinal pathways become hyperexcitable due to a lack of sensory input, which causes tonic disinhibition of descending circuits and spontaneous activity in the dorsal root ganglia (DRG). Spinal excitability can be measured using the H-reflex, in which electrical stimulation of muscle spindle Ia afferents activates spinal motoneurons via the myotatic reflex, as well as the posterior root-muscle (PRM) reflex, which is elicited by transcutaneous stimulation over the dorsal roots and is considered to be half of the H-reflex, excluding the peripheral primary afferents, but with multiple root activation. Spinal excitability has not been measured in amputees but may offer a potential biomarker for PLP. Neuromodulation may restore normal spinal excitability and reduce PLP, thus offering the potential to improve the quality of life in individuals with a lower limb amputation. The results of this study will provide the foundation for future development of a neuroprosthesis to restore spinal excitability and reduce PLP in individuals with a lower limb amputation. Subjects will undergo 5 testing and stimulation sessions in 1 week. An additional 3 days of recording sessions may be necessary if a phantom limb pain episode does not occur during normal testing days.

Specific Aim 1: Quantify spinal excitability. A lack of sensory input results in spinal hyperexcitability through several pathways including tonic disinhibition of descending circuits and spontaneous activity in the DRG. Spinal cord excitability is directly related to reflex modulation; impaired or enhanced reflex modulation indicates abnormal spinal cord excitability. Spinal cord excitability will be determined in people with a lower limb amputation using the H-reflex and posterior root-muscle (PRM) reflex. The H-reflex is elicited with electrical stimulation of peripheral nerves, exciting muscle spindle Ia afferents projecting to spinal motoneurons via the myotatic reflex. Stimulation of the peripheral nerves also elicits a direct motor (M) wave. The PRM reflex is elicited by electrical stimulation of the posterior roots on the back. It is considered to be half of the H-reflex, excluding the peripheral motor efferents, but activates multiple dorsal roots. Reflex amplitude and latency, threshold, recruitment curves, and rate-dependent depression will be measured and compared to intact controls. The investigators hypothesize that H and PRM reflex hyperexcitability will be present in the residual limb of amputees with PLP. These results will provide insight into the role of limb amputation on spinal cord health and excitability.

Specific Aim 2: Characterize the effects of transcutaneous spinal cord stimulation on spinal cord excitability and phantom limb pain.

Neuromodulation of sensorimotor pathways using transcutaneous electrical nerve stimulation (TENS), dorsal root ganglia stimulation (DRGS), and epidural spinal cord stimulation (eSCS) to reduce phantom limb pain have been explored with mixed results. The most promising methods for pain reduction were DRGS or laterally-placed eSCS, indicating that the DRG and dorsal roots are optimal targets for reducing PLP. However, these methods require surgical implantation of electrodes. Transcutaneous spinal cord stimulation (tSCS) is a non-invasive method for stimulating the dorsal roots in a similar way as eSCS. Through activation of the primary afferents, tSCS may inhibit pain pathways and reduce the hyperexcitability that leads to chronic pain. tSCS in people with spinal cord injury has been shown to restore spinal inhibition and reduce H-reflex hyperexcitability. The investigators hypothesize that tSCS can reduce PLP through modulation of sensorimotor pathways. By comparing the H- and PRM reflex excitability recorded from the residual limb before and after each session of tSCS, a potential mechanism of PLP could be elucidated. H- and PRM reflex modulation, and any differences in the extent of modulation for each, can further inform on the mechanisms of tSCS and how it modulates sensorimotor pathways. The investigators will also quantify the subjects' experience of PLP before and after the 5 days of tSCS and correlate their pain experiences with spinal excitability measures. The investigators will use a visual analog scale and the McGill Pain Questionnaire to assess changes in pain perception. The investigators will also use an algometer to determine changes in local pain threshold.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 3

Inclusion Criteria

Participants must be between the ages of 21 and 70 years old.
Participants must have a trans-tibial amputation and phantom limb pain in at least one leg

Exclusion Criteria

Participants must not have any serious disease, disorder, or infection (ex. blood or bone disorder or infection) that could affect their ability to participate in this study.
Female participants of child-bearing potential must not be pregnant or breast feeding, or plan to become pregnant during the course of the study.
Participants must not have any implanted stimulators or pulse generators
Participants must not have any implanted metallic devices in their torso and/or legs
Participants must not have heart disease, including known arrhythmia

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transcutaneous spinal cord stimulation	Transcutaneous spinal cord stimulation	Transcutaneous spinal cord stimulation on lower back for 30-60 minutes for 5 consecutive days.

Primary Outcome Measures

Name	Time	Method
Mean H-reflex Threshold	Day 5	Reflex threshold: stimulation amplitude required to evoke reflex response. The presence of H-reflexes are expected in uninjured individuals.
Mean PRM Reflex Threshold	Day 5	Reflex threshold: stimulation amplitude required to evoke reflex response. Thresholds in uninjured people have been reported to be approximately 30 mA.

Secondary Outcome Measures

Name	Time	Method
Pain Pressure Threshold	Day 5	Pain Pressure Threshold Test using an algometer: minimum force that induces pain, minimum = 0 N, maximum = 444.8 N, a lower threshold indicates hypersensitivity
Phantom Limb Pain Score	Day 5	McGill Pain Questionnaire: minimum = 0, maximum = 78, the higher the pain score the greater the pain
Pain Score	Day 5	Visual analog scale: minimum = 0, maximum = 10, the higher the score the greater the pain

Trial Locations

Locations (2): University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Carnegie Mellon University
🇺🇸
Pittsburgh, Pennsylvania, United States