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?

This trial explores a new method to reduce neuropathic pain in individuals with spinal cord injuries. The treatment, Operant Conditioning of Cutaneous Reflexes, trains the leg's natural reflexes to manage and decrease pain. Participants receive visual feedback as they attempt to change their reflex activity during sessions. The trial seeks individuals who have experienced neuropathic pain in their lower leg for over a year and can stand for at least three minutes, even with assistive devices. As an unphased trial, this study offers a unique opportunity to contribute to innovative pain management research.

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.

What prior data suggests that this reflex training procedure is safe for individuals with spinal cord injury?

Research has shown that training skin reflexes is generally safe and well-tolerated. This treatment involves teaching reflexes in the leg to help reduce nerve pain. Studies have found no major safety concerns with this approach. In past cases, patients experienced improvements in walking and a reduction in foot drop, which is difficulty lifting the front part of the foot.

Although detailed information on side effects is limited, the absence of major safety issues in earlier research suggests that the treatment is manageable for participants. The current study phase continues to explore safety, but previous findings offer a positive outlook on its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about operant conditioning of cutaneous reflexes for neuropathic pain in spinal cord injury because it offers a unique approach by retraining the nervous system to reduce pain. Unlike standard treatments that might rely on medications to manage symptoms, this technique uses visual feedback to help participants actively change their reflex responses. By directly targeting and modifying the reflex pathways, this method could provide a non-drug, personalized way to manage pain, potentially leading to more sustainable and long-term relief for patients.

What evidence suggests that this reflex training is effective for neuropathic pain?

Research has shown that training the body's reflexes can help reduce nerve pain in people with spinal cord injuries. In this trial, participants will undergo Operant Conditioning of Cutaneous Reflexes, which teaches the body to change its automatic responses. Early studies have found that this method can lead to less pain. Specifically, one report noted that people experienced reduced pain with this reflex training. The technique focuses on changing reflexes in the leg, which is believed to help lower pain. While more research is needed, these early results offer promise for those dealing with this type of pain. ^{1 2 3 4 5}

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

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

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trialx.com

trialx.com/clinical-trials/listings/236866/neuropathic-pain-and-operant-conditioning-of-cutaneous-reflexes-after-sci/

Neuropathic Pain and Operant Conditioning of Cutaneous ...

Overview. The purpose of the second part of the study is to examine the effect of reflex training in the leg to decrease neuropathic pain.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC6095771/

Clinical Translation of Spinal Reflex Operant Conditioning

This paper reviews the value of spinal reflexes and the therapeutic promise of spinal reflex operant conditioning protocols.

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05094362

NCT05094362 | Operant Conditioning of Spinal Reflexes ...

The purpose of this study is to validate the capacity of a reflex training system to change the size of the targeted reflex. For this, the researchers are ...

4.

apps.dtic.mil

apps.dtic.mil/sti/trecms/pdf/AD1221822.pdf

Targeted Spinal Cord Plasticity for Alleviating SCI-Related ...

The first case of cutaneous reflex conditioning in individual with mild neuropathic pain has been reported in a conference abstract and ...

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wearesrna.org

wearesrna.org/blog/operant-conditioning-rehabilitation-studies/

Operant Conditioning Rehabilitation Studies | SRNA Blog

Initial results have seen improved walking and lessened foot drop. The third study addresses neuropathic pain after spinal cord injury. People ...