Abstract

Introduction:

Post-stroke pain (PSP) remains a common and profoundly debilitating consequence of stroke, both in terms of a delay in recovery and in substantially reducing quality of life. Both invasive and non-invasive brain stimulation techniques are increasingly being explored as possible treatment modalities for various forms of PSP. This literature review examines the current body of evidence for all forms of neurostimulation for PSP.

Methods:

In this paper, we provide a review of the most recent literature exploring neuromodulation for PSP, covering several key domains: an examination of various PSP subtypes and the underlying mechanisms; a consolidation to date of the literature examining both invasive and non-invasive neuromodulation techniques for forms of PSP, and a discussion of future directions for the field.

Results:

The impact of neuromodulation techniques on PSP populations, focusing primarily on spasticity and central post-stroke pain (CPSP) is discussed.

Conclusion:

To varying degrees, numerous invasive and non-invasive modalities are beginning to be explored for individuals suffering from PSP. While preliminary, there is promising evidence to suggest that neuromodulatory techniques may reduce or ameliorate PSP. Further evidence and large clinical trials are needed to compare these treatments to the standard of care, as well as each other, to optimize outcomes for patients. In a rapidly evolving field, this review helps to provide the current state of neuromodulation in research on PSP.

Introduction

Stroke is one of the most common and disabling neurological disorders. It affects nearly 800,000 individuals each year in the United States alone, with the number is expected to continue rising in the coming decades (1, 2). It is also responsible for a substantial reduction in quality of life and disability-adjusted life years as stroke survivors are burdened with multiple chronic issues such as motor and sensory deficits, cognitive impairment, and pain (3–6). Data suggest that nearly 70% of stroke survivors experience some form of post-stroke pain (PSP), a broad term that encompasses all pain syndromes that occur after stroke, which can include spasticity, complex regional pain syndrome (CRPS), and central post-stroke pain (CPSP). PSP can also negatively impact rehabilitation and delay recovery while simultaneously making recovery more expensive (7).

The current standard of care for PSP includes a multimodal approach of physical/occupational therapies and medications. While physiotherapy can be beneficial for improving of mobility and reducing pain, it can face limitations from patients’ chronic motor deficits or cognitive impairments following stroke, and there is currently limited knowledge on its impact on changes in pain intensity (5, 8). Medications may be helpful in some cases of PSP, but many of the medications, including antidepressants like amitriptyline, anti-inflammatories, and anti-epileptic drugs such as gabapentin and pregabalin, have demonstrated limited or mixed efficacy (5, 6, 9, 10). Further, many of these patients who are treatment-resistant to initial therapy require opioids for pain management, which can lead to dependency (11, 12). Therefore, there is growing interest and need for interventions that can attenuate chronic pain following stroke and improve patients’ quality of life. One such emerging intervention is neuromodulation via multiple brain stimulation techniques.

Neuromodulation techniques, broadly, are those that utilize methods to modify neural activity in a targeted manner to address various neurological conditions. An increasing number of studies indicate that invasive techniques, such as deep brain stimulation (DBS), motor cortex stimulation (MCS), spinal cord stimulator (SCS), and vagus nerve stimulation (VNS), may offer therapeutic benefit in treatment-refractory cases (13–15). While these techniques have shown analgesic properties in a range of neuropsychiatric conditions, including stroke, they are often not feasible options for individuals due to their expense, as well as being invasive surgical procedures (16–18). As such, non-invasive, affordable options are in great demand and are beginning to gain more traction. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcutaneous auricular vagus nerve stimulation (taVNS), and low-intensity focused ultrasound (LIFU) are all generally safe, well-tolerated, affordable non-invasive modalities that, while additional research is still needed, can be beneficial for reducing chronic pain and improving quality of life in stroke patients (18). In the following sections, we will discuss the various types of PSP, the current literature on both invasive and non-invasive neuromodulation techniques for its treatment, proposed mechanisms of action, and future directions for the field.

For this narrative review, we conducted a targeted search of the literature to identify studies evaluating neuromodulation for the treatment of post-stroke pain. The primary search was performed in PubMed, covering the period from 1990 to the present. Search terms were constructed around key concepts related to post-stroke pain (e.g., “post-stroke pain,” “central post-stroke pain,” and “spasticity”) and combined with modality-specific terminology for each intervention (e.g., ((“deep brain stimulation” [Title/Abstract] OR “DBS” [Title/Abstract]) AND (“post stroke pain” [Title/Abstract]) OR (“central post-stroke pain” [Title/Abstract]) OR (“spasticity” [Title/Abstract])). In total, 683 publications were initially identified (DBS: 104; MCS: 62; SCS: 140; VNS: 9; TMS: 287; tDCS: 72; taVNS: 3; LIFU: 6). Advanced filters were used to exclude review articles, focusing only on clinical trials, randomized controlled trials, and meta-analyses. With this filter applied, 131 publications were identified. Eligible publications included studies in which at least one of the above neuromodulation modalities was applied to a form of post-stroke pain. Studies in which neuromodulation was delivered primarily in the context of motor rehabilitation or functional recovery (i.e., not targeting pain outcomes) were excluded. Relevant primary research articles were identified through a supplementary manual review of references from selected articles and prior reviews. Publications were screened for redundancy and relevance to the review topic, with emphasis on studies reporting therapeutic outcomes, mechanistic insights, or emerging applications of neuromodulation in post-stroke pain. In total, 31 articles were included. Of these articles, study rigor was assessed using an unweighted composite score based on sham control, sample size, and study design. Sham-controlled studies received 2 points, studies with a comparator but no sham received 1 point, and uncontrolled studies received 0 points; sample size was scored as 2 points for n50, 1 point for n = 40–49, and 0 points for n < 20. Study design was scored as 2 points for randomized controlled trials, 1 point for prospective non-randomized or cohort studies, and 0 points for retrospective studies, case series, or case reports. Total scores were categorized as high rigor (5–6), moderate rigor (3–4), or low rigor (0–2) (see Tables 1, 2).

Author, YearStimPainTargetParametersOutcome measuresFindingsAEsRigor ScoreNowacki et al., 2025 (47)DBS
n = 39CPSP

Sham controlled: No

Frequency: 1000 Hz

Amplitude: NR

Pulse Width: 90 μs

Duration: 12 mo

No1Niu et al., 2024 (46)DBS
n = 1CPSP

Sham controlled: No

Frequency: 15, 75, 130 Hz

Amplitude: 2–4.75 V

Pulse Width: 50, 60, 90 μs

Duration: 7 mo

Power spectral density varied with pain levels in delta, theta, and gamma bands

DBS modulated pain-related thalamic oscillations; power spectral density changes may serve as quantitative indicators of pain relief

No0Boccard et al., 2013 (53)DBS
n = 85NP

>30% improvement in VAS & McGill Pain Questionnaire

>30% improvement in Short-Form 36 Questionnaire and EuroQol-5D Questionnaire

Some improvement maintained at 1-year follow-up

No3Mallory et al., 2012 (65)DBS
n = 1CPSPNo0Lempka et al., 2017 (68)DBS
n = 9PSP

Beck Depression Inventory

Beck Anxiety inventory

Columbia-Suicide Severity Rating Scale

Montgomery-Asberg Depression Rating Scale

Positive and Negative Affect Schedule

Pain Disability Index

VAS

Short-Form McGill Pain Questionnaire

No significant difference in pain disability or VAS between DBS ON and OFF

Greater improvement in depression symptoms with DBS ON

Improvement in affective pain experience with DBS ON

No change in McGill score

Yes4Gopalakrishnan et al., 2018 (69)DBS
n = 10CPSP

Decrease early N1- restored salience & discrimination

Decrease posterior P2 - reduced anticipatory anxiety

Increase anterior N1 - improved cognitive/emotional regulation (in responders)

No4Jones et al., 2021 (70)DBS
n = 5PSPNo4Franzini, A. et al., 2020 (71)DBS
n = 4CPSP

Pre-op VAS: 9 (range 8–10)

Short-term follow-up (1 week): VAS 3 (range 0–6)

Long-term (mean 5.88 y): VAS 5.5 (range 3–8)

No0Guo et al., 2022 (75)MCS
n = 21CPSP

Thalamic stroke group:

Decrease in VAS pain scores

Reduction in neuropathic pain

Improved sleep quality

Extra-thalamic stroke group:

Modest VAS pain reduction

No1Zhang et al., 2017 (76)MCS
n = 16CPSPYes0Zhang et al., 2018 (77)MCS
n = 16CPSP

Decrease in VAS pain score

Decrease in total Neuropathic Pain Symptom Inventory score

Relief of burning pain associated with positive outcomes

No0Lefaucher et al., 2011 (83)MCS
n = 6CPSP

Sham controlled: Yes

Frequency: 40 Hz

Amplitude: 2 V

Pulse width: 60 μs

Duration: 12 mo

Randomized phase: All clinical scores decreased in MCS ON vs. OFF

Open follow-up: Significant improvement in all scores

Medication Quantification Scale: greater effect on affective component of pain

Yes4Busch et al., 2024 (86)SCS
n = 2CPSP

Sham controlled: No

Frequency: 50 Hz

Pulse width: 1000 μs

Duration: NR

Yes0Zhang et al., 2024 (88)SCS
n = 1CPSPNo0Hosomi et al. 2022 (89)SCS
n = 166CPSP

Cervical

Lower thoracic

Midline cervical

Upper cervical

Sham controlled: No

Frequency: 25–50 Hz

Pulse width: 210 μs

Duration: Median 24 mo

Mean pain score decreased 40% immediately after stimulation and maintained until follow-up (24–63 months)

Around 60% of patients had ≥30% pain reduction at both time points

Yes2Tanei et al., 2023 (90)SCS
n = 1CPSP

Cervical spine 3–5

Thoracic spine 8–9

No0

Literature investigates invasive brain stimulation techniques for post-stroke pain.

AEs, adverse events; ALIC, anterior limb of internal capsule; CPSP, central post-stroke pain; DBS, deep brain stimulation; IC, internal capsule; M1, primary motor cortex; MAS, modified Ashworth scale; MCS, motor cortex stimulation; NP, Neuropathic Pain; NR, not recorded; NRS, numerical rating scale; PSP, post-stroke pain; PVG, periventricular gray; SCS, spinal cord stimulation; VAS, visual analog scale for pain; VS, ventral striatum. Duration is defined by the time of the final follow-up for the study. Studies are coded by rigor scores: low (orange, 0–2), medium (green, 3–4), and high (blue, 5–6).

Author, YearStimPainTargetParametersMeasuresFindingsAEsRigor ScoreWang et al., 2025 (27)TMS
n = 85SP

MAS

FMA for Upper Extremity

No6Hosomi et al., 2013 (49)TMS
n = 21CPSP

Sham controlled: No

Number of sessions: 1

Frequency: 5 Hz

Pulse number: 500

Intensity: 120% resting MT

Duration: 10 min (10s stimulation, 50s ISI)

8 of 21 patients had ≥30% pain reduction

Responders showed lower baseline intracortical facilitation compared to controls and nonresponders, which increased after rTMS

No2Chen et al., 2021 (112)TMS
n = 32SP

MAS

Modified Tardieu Scale

Shear Wave Velocity

Motor-evoked Potential

Barthel Index

Improvement in MAS, Modified Tardieu Scale, shear wave velocity, and Barthel Index in cerebellar iTBS compared to sham group

No5Kobayashi et al., 2015 (114)TMS
n = 18CPSP

At week 12, 61.1% of participants were classified as responders: 5 showed >70% pain reduction, 6 showed 40–69% reduction, and 7 showed <40% reduction on the VAS

No1Hasan et al., 2014 (115)TMS
n = 14CPSP

Improved cold detection threshold

Modest NRS pain reduction (from 7.0 to 6.3)

Greater improvement in warm detection is associated with larger reductions in pain

No1Ohn et al., 2012 (116)TMS
n = 22CPSP

Sham controlled: No

Number of sessions: 5

Frequency: 10 Hz

Pulse number: 1000

Intensity: 90% resting MT

Duration: 50 min (5 s stimulation, 55 s ISI)

14 responders showed significant reductions in VAS scores, lasting 2 weeks

Lower baseline depression scores were associated with greater pain relief

Higher ipsilesional superior thalamocortical tract integrity was correlated with greater VAS

Decreased activity in secondary somatosensory cortex, insula, prefrontal cortex, and putamen

No2Ojala et al., 2022 (118)TMS
n = 17CPSP

NRS

Cold Pressure Test

Brief Pain Inventory

Disabilities of the Arm, Shoulder, and Hand

Pain Anxiety Symptom Scale

Health-related QoL

Beck Depression Inventory

rTMS to S2 produced ≥30% long-term pain reduction in 18% of participants

All stimulations yielded similar short-term relief (~17–20%), likely placebo effect

Only S2 stimulation showed significant long-term effects

Cold pressor test revealed significantly reduced pain sensitivity

No4de Oliveira et al., 2014 (119)TMS
n = 21CPSP

Sham controlled: Yes

Number of sessions: 10

Frequency: 10 Hz

Pulse number: 1250

Intensity: 120% resting MT

Duration: 12.5 min (5 s stimulation, 25 s ISI)

VAS

Neuropathic Pain Questionnaire

McGill Pain Questionnaire

HARS

HDRS

36-Item Short-form Health Survey

No5Molero-Chamizo et al., 2021 (42)tDCS
n = 3SP

Sham controlled: Yes

Number of sessions: 5

Intensity: 1.5 mA

Duration: 20 min

No3Bae et al., 2014 (129)tDCS
n = 14CPSP

Sham controlled: Yes

Number of sessions: 9

Intensity: 2 mA

Duration: 20 min

VAS

Pain from cold and heat

Skin Temperature

Reduced VAS scores and skin temperature

Increased cold pain/sensation thresholds

Decreased heat pain/warmth thresholds

No4Halakoo et al., 2021 (131)tDCS
n = 32SP

Sham controlled: Yes

Number of sessions: 10

Intensity: 2 mA

Duration: 20 min

No5Ochi et al., 2013 (132)tDCS
n = 18SP

Sham controlled: Yes

Number of sessions: 10

Intensity: 1 mA

Duration: 10 min

No4Del Felice et al., 2013 (133)tDCS
n = 10SP

Sham controlled: Yes