tVNS and Spinal Cord Injury: What the Evidence Actually Shows

Why This Article?

Spinal cord injury (SCI) remains one of the most devastating neurological conditions. In the United Kingdom, approximately 4,400 new cases occur per year, with an estimated 105,000 individuals living with SCI. Lifetime costs are conservatively estimated at a mean of £1.12 million per case.

SCI causes far more than motor impairment. The disruption of spinal pathways produces motor paralysis, sensory loss, autonomic dysfunction (cardiovascular instability, neurogenic bladder and bowel, thermoregulatory failure), neuropathic pain, spasticity, and a high burden of depression and anxiety. For many individuals, the autonomic consequences are rated as more disabling than the loss of movement itself.

A critical concept in modern SCI science is that "clinically complete" injuries are not necessarily neurologically complete. Electrophysiological studies have demonstrated that residual neural connections often exist even when no clinically detectable function is present. These residual pathways represent a potential substrate for neuromodulation-enhanced recovery.

Current rehabilitation has well-recognised limitations, particularly in chronic SCI where spontaneous neurological recovery has plateaued. There is a significant unmet need for adjunctive therapies that can enhance neuroplasticity and recruit residual neural pathways.

Vagus nerve stimulation (VNS) paired with rehabilitation has emerged as precisely such an approach. Following its success in stroke rehabilitation (FDA-approved implanted Vivistim system), VNS has now been demonstrated to enhance motor recovery in SCI, with a landmark trial published in Nature in 2025. Transcutaneous vagus nerve stimulation (tVNS) offers a non-invasive route to the same mechanism.

Anatomical Concepts distributes the tVNS® system in the UK and Ireland. This article provides clinicians with a thorough, honest review of the evidence for vagus nerve stimulation in SCI rehabilitation.

A note on transparency: The evidence for VNS in SCI is at a much earlier stage than for stroke. There is one landmark RCT of implanted closed-loop VNS (published in Nature, 2025), a small number of preclinical studies, and very limited data on transcutaneous VNS specifically in SCI. This article explains what we know, what we can reasonably infer, and what remains to be demonstrated.

How VNS Enhances SCI Rehabilitation

The Paired VNS Paradigm

The core mechanism is the same as in stroke rehabilitation. Brief electrical stimulation of the vagus nerve, delivered when a patient performs a rehabilitation movement, triggers rapid release of neuromodulators from brainstem nuclei:

Norepinephrine from the locus coeruleus, enhancing signal-to-noise ratio in active neural circuits and facilitating long-term potentiation.

Acetylcholine from the nucleus basalis of Meynert, essential for cortical map reorganisation and specificity of plasticity.

When VNS is delivered at the moment a patient performs a successful movement, the simultaneous release of these neuromodulators creates a "synaptic eligibility window" during which active neural circuits are preferentially strengthened.

How this applies to SCI: In incomplete SCI, residual corticospinal tract fibres and propriospinal connections exist but may be insufficient to generate functional movement. VNS-enhanced plasticity could strengthen these residual pathways, recruiting them into functional motor circuits. The brain is intact but the spinal "bridge" is damaged. Strengthening cortical motor representations and corticospinal connectivity through paired VNS may help maximise use of whatever spinal pathways remain.

Autonomic Modulation

SCI at or above T6 disrupts supraspinal control of the sympathetic nervous system. The vagus nerve, as the principal parasympathetic pathway, remains intact. Whether tVNS can positively modulate autonomic dysfunction (rather than merely being safe) requires further investigation, but the cardiovascular safety data is reassuring (see below).

Anti-Inflammatory Effects

SCI involves significant neuroinflammation. Remarkably, 76% of chronic SCI patients have elevated C-reactive protein. VNS engages the cholinergic anti-inflammatory pathway. Chen et al. (2022) demonstrated in a rat SCI model that VNS promoted conversion of pro-inflammatory M1 microglia to anti-inflammatory M2 microglia, reducing TNF-alpha, IL-1beta, and IL-6 while increasing IL-10. Chen et al. (2023) showed that VNS prevents blood-spinal cord barrier disruption after SCI by restricting microglia-derived TNF-alpha.

Neuropathic Pain Modulation

Neuropathic pain affects 40 to 70% of individuals with SCI. The disruption of descending inhibitory pathways (serotonergic from raphe nuclei, noradrenergic from locus coeruleus) contributes to central sensitisation. VNS activates these same brainstem nuclei, potentially partially restoring descending inhibitory tone. No published clinical studies have examined tVNS for neuropathic pain in SCI, but the mechanistic rationale is compelling.

Depression and Mood

Depression affects 20 to 30% of individuals with SCI and is independently associated with poorer rehabilitation outcomes. tVNS has established evidence for depression (it is a CE-marked indication), and the mechanistic pathway is the same regardless of the cause of depression.

KEY POINT: VNS may benefit SCI through multiple mechanisms: neuroplasticity enhancement during rehabilitation, anti-inflammatory effects, autonomic modulation, pain pathway modulation, and mood improvement. The clinical evidence to date supports the neuroplasticity mechanism most strongly, with the landmark Nature 2025 trial demonstrating motor recovery gains.

Why the Ear? The Anatomy Behind tVNS

The auricular branch of the vagus nerve (ABVN) provides the anatomical basis for transcutaneous stimulation. The cadaver dissection study by Peuker and Filler (2002) established that the cymba conchae has 100% vagal innervation, compared with approximately 45% at the tragus. The fMRI study by Frangos et al. (2015) confirmed that cymba conchae stimulation activates the NTS, locus coeruleus, dorsal raphe, amygdala, and nucleus accumbens.

This anatomical precision matters: stimulation at the wrong ear site does not reliably activate the brainstem pathways that drive the therapeutic effect.

The Landmark Study: VNS for Cervical SCI (Kilgard et al., 2025, Nature)

This is the most important study in the field and warrants detailed examination.

19 individuals with chronic, incomplete cervical SCI received an implanted VNS device and underwent 12 weeks (36 sessions) of gamified rehabilitation with closed-loop VNS (stimulation bursts triggered by successful movements) or sham.

• Primary outcome (GRASSP): Mean improvement of 4.1 ± 1.5 points (p = 0.01). 42% achieved clinically meaningful improvement (≥6 points).
• Pinch force: Mean increase of 393% (p = 5 × 10⁻⁸). 18 of 19 participants improved.
• Wrist torque: Mean increase of 152% (p = 0.007).
• Hand function (Jebsen-Taylor): Mean improvement of 7.5 points (p = 0.03).
• Greater response in motor incomplete injuries: AIS C/D: 54% responders. AIS B: 17% responders.
• Untrained arm also improved, suggesting generalisation of plasticity effects.

The critical finding: Rehabilitation alone (sham group) produced no meaningful improvements. In chronic SCI, closed-loop VNS created gains where rehabilitation alone produced none.

Safety: Zero serious device-related adverse events across 760 patient visits and 3.7 million VNS pulses. No autonomic dysreflexia episodes. No changes in heart rate, blood pressure, or respiratory rate between groups.

A Phase 3 pivotal trial of 70 participants at multiple US centres is planned.

KEY POINT: This Nature 2025 study provides the first RCT evidence that VNS paired with rehabilitation produces clinically meaningful improvements in upper limb function in chronic incomplete cervical SCI. The results were arguably more dramatic than in stroke: rehabilitation alone produced no gains, whereas VNS-paired rehabilitation created significant improvements.

The Stroke Parallel: Why It Matters

The VNS paired rehabilitation paradigm was proven first in stroke. The Dawson et al. (2021) Lancet trial demonstrated that implanted VNS paired with rehabilitation produced significantly greater motor recovery in chronic stroke (47% vs 24% clinically meaningful response, p=0.0098), leading to FDA approval of Vivistim in August 2021.

The mechanism is fundamentally the same in SCI. What differs is the neural substrate: in stroke, the brain is damaged but the spinal cord is intact; in SCI, the brain is intact but the spinal "bridge" is damaged. VNS acts primarily at the supraspinal level, strengthening cortical motor representations that project through residual spinal pathways.

What About Transcutaneous VNS Specifically?

This is where complete transparency is essential.

There are no published clinical studies of transcutaneous VNS for motor recovery in spinal cord injury. The landmark Kilgard et al. (2025) trial used an implanted device. Only one registered trial (NCT06493071) examines transcutaneous VNS in SCI, addressing depression and inflammation rather than motor function.

The rationale for tVNS in SCI motor recovery is based on:

1. The established efficacy of implanted VNS for SCI (Kilgard et al. 2025)
2. The evidence that tVNS activates the same brainstem pathways as implanted VNS (Frangos et al. 2015)
3. The evidence that tVNS enhances motor recovery in stroke (multiple RCTs, meta-analyses)
4. The shared neuroplasticity mechanism

This represents strong mechanistic inference, but not direct clinical evidence. The distinction between precisely paired implanted VNS and continuous/duty-cycle transcutaneous VNS is also important: the implanted approach triggers stimulation at the exact moment of successful movement, while standard tVNS is delivered continuously during rehabilitation sessions.

Combination with Transcutaneous Spinal Cord Stimulation

Anatomical Concepts also distributes the Stim2Go device for transcutaneous spinal cord stimulation (tSCS). The theoretical rationale for combining tVNS and tSCS is compelling:

tVNS acts above the lesion: Enhancing supraspinal plasticity, strengthening cortical motor representations, creating synaptic eligibility windows.

tSCS acts below the lesion: Modulating spinal circuit excitability, normalising reflex circuits, enhancing motoneuron pool recruitment.

The combination addresses both levels of the neuraxis simultaneously. During rehabilitation, tVNS would prime cortical networks while tSCS primes spinal networks, with the patient's active movement providing the activity-dependent signal.

No published studies have examined this specific combination. However, in stroke, combining taVNS with tDCS produced additive benefits for gait recovery (Wang et al., 2024, n=169), supporting the principle that combining neuromodulation modalities can enhance outcomes.

Stimulation Parameters

No SCI-specific tVNS parameter studies exist. Based on the stroke rehabilitation literature, reasonable starting parameters would be:

Parameter	Suggested Range
Frequency	25 to 30 Hz
Pulse width	200 to 300 µs
Intensity	Titrated to sensory threshold (0.1 to 5 mA)
Delivery	Continuous or duty cycle during rehabilitation
Session duration	30 to 60 minutes
Schedule	3 to 5 sessions per week
Treatment duration	Minimum 6 to 12 weeks
Site	Left cymba conchae

Important caveat: These parameters are extrapolated from stroke trials. The optimal parameters for tVNS in SCI may differ.

Safety Considerations for SCI

Autonomic Dysreflexia

The principal safety concern. The evidence is reassuring:

• Sachdeva et al. (2020): VNS did not trigger or exacerbate autonomic dysreflexia in a rat model of complete high-thoracic SCI
• Kilgard et al. (2025): Zero episodes across 760 patient visits and 3.7 million VNS pulses
• Parameters used deliver 100 times less current than those approved for epilepsy

Cardiovascular Instability

Intermittent VNS at therapeutic parameters produces only transient, mild heart rate changes that resolve immediately. Cardiac monitoring is prudent during initial sessions, particularly with pre-existing bradycardia.

Standard Contraindications

Implanted cardiac devices, active ear infection, pregnancy, caution with cardiac arrhythmias.

Regulatory and Access Context

The tVNS® E device (tVNS Technologies GmbH, Germany) holds Class IIa certification under EU-MDR 2017/745. Spinal cord injury is not a specific CE-marked indication, but the device is approved for neurological conditions and its application in SCI would be within the scope of clinical judgment.

Vivistim (implanted VNS): FDA-approved for chronic ischaemic stroke (2021). Not approved for SCI; Phase 3 trial planned.

NICE has not published guidance on VNS for SCI.

What We Don't Yet Know

No published clinical evidence for tVNS in SCI motor recovery. All human motor evidence uses implanted devices.

Very small sample sizes. The landmark trial enrolled 19 participants.

Continuous vs closed-loop delivery. Whether standard tVNS (continuous/duty-cycle) can achieve comparable benefit to precisely paired implanted VNS is undemonstrated for SCI.

Optimal parameters for SCI. No parameter studies exist.

Which SCI patients benefit most. AIS C/D showed greater response than AIS B, but subgroups are underpowered.

Long-term durability. Unknown beyond the 12-week treatment period.

Autonomic, pain, and spasticity outcomes. No clinical data; mechanistic rationale only.

Combination with tSCS. Theoretical rationale only; no empirical evidence.

Practical Guidance for Clinicians

Candidate Selection (Provisional)

• Adults with incomplete cervical SCI (AIS B, C, or D) who have plateaued with standard rehabilitation
• Individuals willing to engage in intensive, structured rehabilitation exercises alongside stimulation
• Those with depression or pain as comorbidities may benefit additionally
• Absence of cardiac pacemakers or implanted devices
• Caution with pre-existing bradycardia or injuries at/above T6

Treatment Protocol (Provisional)

• 25 to 30 Hz, 200 to 300 µs pulse width, intensity titrated to sensory threshold, left cymba conchae
• Deliver during rehabilitation exercises (concurrent stimulation with task-specific practice)
• 30 to 60 minutes per session, 3 to 5 sessions per week, minimum 6 to 12 weeks
• High-intensity, task-specific practice with high repetition counts (300+ per session)
• Heart rate and blood pressure monitoring at initial sessions

What to Tell Patients

• VNS paired with rehabilitation has been shown to produce significant motor recovery in chronic SCI in a landmark Nature trial using an implanted device. Transcutaneous VNS offers a non-invasive route to the same mechanism.
• The transcutaneous evidence is at an early stage. The approach is supported by strong mechanistic rationale and evidence from stroke rehabilitation, but direct clinical evidence for tVNS in SCI is very limited.
• Engagement in rehabilitation exercises during stimulation is essential. VNS without concurrent rehabilitation does not produce benefit.
• The safety profile is favourable, including in SCI populations with autonomic vulnerability.
• This is an honest, evolving area of clinical practice where the evidence is promising but not yet definitive.

Conclusion

The evidence for vagus nerve stimulation in spinal cord injury has reached an important inflection point. The Kilgard et al. (2025) Nature trial is a landmark: the first RCT to demonstrate that VNS paired with rehabilitation produces meaningful motor recovery in chronic incomplete cervical SCI, in a population where rehabilitation alone produced no gains.

For transcutaneous VNS specifically, the evidence is at an earlier stage. The mechanistic rationale is strong: tVNS activates the same brainstem pathways that drive the neuroplasticity-enhancing effects demonstrated with implanted VNS. The evidence from stroke rehabilitation confirms that transcutaneous delivery can achieve clinically meaningful outcomes. But direct clinical evidence for tVNS in SCI motor recovery does not yet exist.

For clinicians working with individuals who have cervical SCI and are seeking adjunctive therapies, tVNS is a reasonable option to consider, used alongside intensive task-specific practice, with honest communication about the current evidence stage. The combination of tVNS (supraspinal plasticity) with tSCS (spinal plasticity) represents a particularly compelling frontier.

The evidence is evolving rapidly. The Phase 3 pivotal trial of closed-loop VNS for SCI and the NCT06493071 trial of taVNS for SCI inflammation and depression will significantly update the landscape.

Related Literature

1. Peuker ET, Filler TJ. The nerve supply of the human auricle. Clin Anat. 2002;15(1):35-37.

2. Frangos E, Ellrich J, Komisaruk BR. Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul. 2015;8(3):624-636.

3. Ganzer PD, et al. Closed-loop neuromodulation restores network connectivity and motor control after spinal cord injury. eLife. 2018;7:e32058.

4. Redgrave J, et al. Safety and tolerability of transcutaneous vagus nerve stimulation in humans: a systematic review. Brain Stimul. 2018;11(6):1225-1238.

5. Darrow MJ, Torres M, Sosa MJ, et al. Vagus nerve stimulation paired with rehabilitative training enhances motor recovery after bilateral spinal cord injury. Neurorehabil Neural Repair. 2020;34(3):200-209.

6. Sachdeva R, Krassioukov AV, Bucksot JE, Hays SA. Acute cardiovascular responses to vagus nerve stimulation after experimental spinal cord injury. J Neurotrauma. 2020;37(9):1149-1155.

7. Dawson J, et al. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB). Lancet. 2021;397(10284):1545-1553.

8. Chen Y, et al. Vagus nerve stimulation reduces neuroinflammation through microglia polarization regulation to improve functional recovery after spinal cord injury. Front Neurosci. 2022;16:813472.

9. Bloom O, Tracey KJ, Pavlov VA. Exploring the vagus nerve and the inflammatory reflex for therapeutic benefit in chronic spinal cord injury. Curr Opin Neurol. 2022;35(2):249-257.

10. Chen Y, et al. Vagus nerve stimulation prevents endothelial necroptosis to alleviate blood-spinal cord barrier disruption after spinal cord injury. Mol Neurobiol. 2023;60:5434-5449.

11. Fallahi MS, et al. Application of vagus nerve stimulation in spinal cord injury rehabilitation. World Neurosurg. 2023;174:20-30.

12. Gao Y, et al. Vagus nerve stimulation paired with rehabilitation for motor function after stroke: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2023;94(4):257-266.

13. Wang L, et al. Efficacy of combined tVNS and tDCS on gait in 169 subacute stroke patients. J Rehabil Med. 2024;56:jrm40348.

14. Kilgard MP, Epperson JD, Adehunoluwa EA, et al. Closed-loop vagus nerve stimulation aids recovery from spinal cord injury. Nature. 2025;643(8073):1030-1036.

15. Addo JJA, Neifert CL, Danaphongse TTT, et al. Temporal parameters determine the efficacy of vagus nerve stimulation directed neural plasticity. Neurorehabil Neural Repair. 2025.

16. Hays SA, et al. Enhancing neuroplasticity via vagus nerve stimulation to improve urinary dysfunction after spinal cord injury: a perspective. Bioelectron Med. 2025.

17. Tanaka T, Gokden M, Landes RD. Can transcutaneous vagus nerve stimulation be effective after rats' spinal cord injury? Cureus. 2026;18(2).

18. McDaid D, et al. Understanding and modelling the economic impact of spinal cord injuries in the United Kingdom. Spinal Cord. 2019;57:778-788.

Review current as of April 2026. The evidence for VNS in SCI is evolving rapidly. The Phase 3 pivotal trial of closed-loop VNS for SCI and the NCT06493071 trial of taVNS for SCI will significantly update the landscape.