Reflex Training for Neuropathic Pain in Spinal Cord Injury

Overseen By Blair Dellenbach, MSOT

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Motoneuron injury, Cardiac condition, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 38

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The purpose of the second part of the study is to examine the effect of reflex training in the leg to decrease neuropathic pain. For this, the researchers are recruiting 15 individuals with neuropathic pain due to spinal cord injury to participate in the reflex training procedure. The study involves approximately 50 visits with a total study duration of about 6.5 months (3 months for baseline and training phases followed by 1 month and 3 month follow-up visits).

Will I have to stop taking my current medications?

The trial requires that you keep taking your current medications without any changes for at least 3 months. If you are on anti-spasticity medication, you can continue using it as usual.

Is reflex training for neuropathic pain in spinal cord injury safe?

Research on reflex training, also known as operant conditioning of spinal reflexes, has been conducted in animals and humans, showing promising results without significant safety concerns. Studies have demonstrated that this method can safely modify reflexes in people with spinal cord injuries, suggesting it is generally safe for human use. ^{1 2 3 4 5}

How does the Reflex Training Procedure treatment differ from other treatments for neuropathic pain in spinal cord injury?

The Reflex Training Procedure is unique because it uses operant conditioning to modify spinal reflexes, promoting plasticity (the ability to change and adapt) in the nervous system, which can improve motor function and potentially reduce pain. Unlike traditional treatments that may rely on medication, this approach focuses on retraining the body's reflex pathways to enhance recovery. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Operant Conditioning of Cutaneous Reflexes for neuropathic pain in spinal cord injury?

Research on operant conditioning of spinal reflexes shows promising results in both animals and humans, indicating that this approach can help modify reflex behaviors through brain and spinal cord plasticity. This suggests potential benefits for managing neuropathic pain in spinal cord injury patients. ^{2 8 10 11 12}

Who Is on the Research Team?

Aiko Thompson, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for individuals with neuropathic pain in the lower leg due to spinal cord injury. They must be stable over a year post-injury, able to stand for at least 3 minutes, and on steady medication for 3 months. Excluded are those with motoneuron injuries, heart conditions, cognitive impairments or complete lack of sensation around the foot.

Inclusion Criteria

My neuropathic pain affects my lower leg.

My spinal cord injury has been stable for over a year.

My current medication will stay the same for the next 3 months.

Exclusion Criteria

I use electrical stimulation on my leg every day.

I cannot feel anything in my foot.

I have severe nerve pain or tingling that is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Participants undergo baseline assessments including cutaneous reflex examination and sensation assessment

3 months

6 visits (in-person)

Conditioning

Participants complete 30 conditioning sessions to alter cutaneous reflexes and reduce neuropathic pain

3 months

30 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Operant Conditioning of Cutaneous Reflexes

Trial Overview The study tests reflex training aimed at reducing neuropathic pain after spinal cord injury. It involves about 50 sessions over roughly 6.5 months including baseline assessment, training phase and follow-up visits at one month and three months post-training.

How Is the Trial Designed?

Group I: Operant Conditioning of Cutaneous Reflexes Experimental Treatment 1 Intervention

Each participant completes 6 baseline sessions and 30 conditioning sessions. In each of the 30 conditioning sessions, while the participant is standing nerves in the lower leg and ankle are stimulated to activate the reflex. The participant attempts to change the reflex activity based on visual feedback. In this way the cutaneous reflex (skin reflex) will be changed to decrease neuropathic pain resulting from spinal cord injury.

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

Rats with spinal cord injuries of varying severity exhibited similar reductions in pain sensitivity, indicating that the severity of the injury does not necessarily correlate with the level of pain experienced.

Increased wind-up responses, which reflect central excitability, were observed in all injured rats, with more severe injuries showing greater increases, suggesting that wind-up measurements can effectively assess changes in pain mechanisms after spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal study of wind-up responses after graded spinal cord injuries in the adult rat. Redondo Castro, E., Udina, E., Verdú, E., et al.[2013]

The newly designed Overground System allows for a more accurate assessment of pain-like behaviors in response to cold and mechanical stimuli in animals with spinal cord injury, addressing issues of hyperreflexia that can confound traditional testing methods.

Results showed that after spinal cord injury, animals exhibited significant changes in crossing behavior over different surfaces, indicating adaptive decision-making in response to pain stimuli, which can help tailor pain assessment methods for different types of hypersensitivity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel affective-motivational-based Overground System for detecting spinal cord injury-associated thermal and mechanical hypersensitivity in rats. Dugan, EA., Sagen, J.[2019]

Individuals with spinal cord injuries often experience neuropathic pain during intensive gait rehabilitation, suggesting that pain and rehabilitation may not be independent issues as previously thought.

Research indicates that nociception (pain perception) and motor learning may share common neural mechanisms, which could impact rehabilitation strategies and outcomes for patients with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury. Mercier, C., Roosink, M., Bouffard, J., et al.[2018]

Operant conditioning of spinal reflexes has evolved over 35 years from basic science to a promising rehabilitation therapy for spinal cord injuries, showing significant potential for enhancing nervous system plasticity.

Initial studies in both animal models and humans indicate that reflex conditioning can lead to exciting therapeutic outcomes, highlighting the importance of basic research in informing clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal reflexes: from basic science to clinical therapy. Thompson, AK., Wolpaw, JR.[2022]

In a rat model of spinal cord injury (SCI), different pain assessment methods revealed that brainstem reflexes and aversive behaviors were more indicative of pain at the level of injury, while below-level stimulation primarily triggered spastic reflexes rather than pain-like responses.

The study suggests that traditional spinal reflex measures are not suitable for assessing pain in SCI models, and emphasizes the importance of using cortical-dependent methods, like the place escape/avoidance paradigm (PEAP), for accurately evaluating central pain mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spinal-, brainstem- and cerebrally mediated responses at- and below-level of a spinal cord contusion in rats: evaluation of pain-like behavior. Baastrup, C., Maersk-Moller, CC., Nyengaard, JR., et al.[2021]

Operant conditioning protocols can effectively modify spinal reflexes, which are fundamental behaviors, providing valuable insights into the mechanisms of learning.

These protocols can also promote neural plasticity, potentially aiding in the recovery of motor skills like walking in individuals with spinal cord injuries or related disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The simplest motor skill: mechanisms and applications of reflex operant conditioning. Thompson, AK., Wolpaw, JR.[2021]

In a study involving 17 chronic spinal cord-injured patients, operant conditioning successfully reduced hyperactive biceps brachii spinal stretch reflexes (SSRs) over 24 training sessions, demonstrating a significant decrease in SSRs (P < 0.001) compared to control subjects.

The reduction in SSRs persisted for up to 4 months after training ended, indicating that operant conditioning can be an effective long-term intervention for managing altered reflexes in spinal cord injury patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal stretch reflexes in patients with spinal cord injuries. Segal, RL., Wolf, SL.[2022]

Operant-conditioning protocols that reward specific electromyographic responses can effectively modify spinal reflex pathways, leading to changes in reflex activity and associated behaviors in both animals and humans.

In individuals with partial spinal cord injuries, these conditioning techniques can enhance locomotion and promote widespread beneficial plasticity in the nervous system, suggesting a promising therapeutic approach for rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted neuroplasticity for rehabilitation. Thompson, AK., Wolpaw, JR.[2018]

In individuals with spinal cord injury (SCI) and spasticity, vibratory stimulation effectively inhibited the tibialis anterior cutaneous reflex (Pl-TA CR) during both rest and controlled plantarflexion, indicating a potential therapeutic approach for managing spasticity.

Transcutaneous electrical nerve stimulation (TENS) was found to inhibit Pl-TA CR activity only during the hold phase of plantarflexion in SCI spastic subjects, suggesting that different modalities may have specific effects on reflex activity and could be useful in neurorehabilitation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Afferent stimulation inhibits abnormal cutaneous reflex activity in patients with spinal cord injury spasticity syndrome. Gómez-Soriano, J., Serrano-Muñoz, D., Bravo-Esteban, E., et al.[2018]

Paired associative stimulation (PAS) showed promising results in reducing severe drug-resistant neuropathic pain in a 50-year-old man with spinal cord injury, with pain scores decreasing by 44% after two weeks of therapy.

The therapy not only alleviated pain but also improved hand motor function and quality of sleep, suggesting that PAS may modulate pain pathways at the spinal cord level and could be a valuable adjunct treatment for neuropathic pain following spinal cord injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report. Vaalto, S., Nyman, AL., Shulga, A.[2021]

Functional electrical stimulation (FES) of the common peroneal nerve has been effective in treating foot drop in patients with central nervous system (CNS) lesions, demonstrating the potential for recovery through nerve stimulation.

Initial studies on operant conditioning of the soleus H-reflex in healthy adults (n=5) show promising results, with reflex size increasing by 16-36% over 2-3 months, indicating that spinal reflex conditioning may enhance plasticity in the human nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation in spinal circuits and corticospinal connections following nerve stimulation and operant conditioning. Thompson, AK., Stein, RB., Chen, XY., et al.[2020]

Individuals with spinal cord injury (SCI) showed a significantly higher response to noxious heat stimuli compared to non-disabled controls, indicating heightened spinal excitability, with 70-77% of SCI participants responding to laser stimuli.

The study found that spasticity was linked to increased reflex responses in SCI patients, while neuropathic pain did not correlate with reflex behavior, suggesting that laser-evoked withdrawal reflexes could be useful for assessing maladaptive spinal processing and the effectiveness of treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noxious radiant heat evokes bi-component nociceptive withdrawal reflexes in spinal cord injured humans-A clinical tool to study neuroplastic changes of spinal neural circuits. Franz, S., Heutehaus, L., Tappe-Theodor, A., et al.[2023]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Longitudinal study of wind-up responses after graded spinal cord injuries in the adult rat. [2013]

2. England pubmed.ncbi.nlm.nih.gov

A novel affective-motivational-based Overground System for detecting spinal cord injury-associated thermal and mechanical hypersensitivity in rats. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Promoting Gait Recovery and Limiting Neuropathic Pain After Spinal Cord Injury. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal reflexes: from basic science to clinical therapy. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Spinal-, brainstem- and cerebrally mediated responses at- and below-level of a spinal cord contusion in rats: evaluation of pain-like behavior. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

The simplest motor skill: mechanisms and applications of reflex operant conditioning. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Operant conditioning of spinal stretch reflexes in patients with spinal cord injuries. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted neuroplasticity for rehabilitation. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Afferent stimulation inhibits abnormal cutaneous reflex activity in patients with spinal cord injury spasticity syndrome. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Analgesic effect of paired associative stimulation in a tetraplegic patient with severe drug-resistant neuropathic pain: a case report. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Modulation in spinal circuits and corticospinal connections following nerve stimulation and operant conditioning. [2020]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Noxious radiant heat evokes bi-component nociceptive withdrawal reflexes in spinal cord injured humans-A clinical tool to study neuroplastic changes of spinal neural circuits. [2023]