Central Post-stroke Pain

Original Editor - Chioma Clara Okeakpu

Top Contributors - Shailly Yadav, Chioma Clara Okeakpu, Vidya Acharya, Alexandra Stead and Lucinda hampton  

Page Summary

• Central post-stroke pain (CPSP), or Dejerine-Roussy syndrome, is central neuropathic pain from a vascular lesion of the central nervous system, causing contralateral somatosensory deficits.
• CPSP affects an estimated 8% to 35% of stroke patients, most often emerging within 1 to 3 months, and follows thalamic or spinothalamic tract damage.
• Diagnosis of CPSP requires excluding nociceptive, psychogenic and peripheral neuropathic pain, supported by history, sensory testing and computed tomography (CT) or magnetic resonance imaging (MRI).
• Management is individualised and multidisciplinary; drugs such as amitriptyline, lamotrigine and gabapentinoids give partial relief, neuromodulation shows moderate benefit, and physiotherapy evidence for pain reduction remains limited.

Introduction

Central post-stroke pain (CPSP), also known as Dejerine-Roussy syndrome, is a form of central neuropathic pain that arises from a vascular lesion of the central nervous system. It typically produces somatosensory deficits contralateral to the stroke lesion. Central neuropathic pain can also follow spinal cord injury or multiple sclerosis, but stroke is its most common cause worldwide.

CPSP resembles thalamic pain syndrome, but its neural involvement is broader: damage may extend beyond the thalamus to affect the spinothalamic and trigeminothalamic tracts, both of which carry pain signals through the central nervous system (CNS). Partial damage to the spinothalamic tract (STT) carries a higher risk of CPSP than complete damage to the same tract.

CPSP can present spontaneously or on induction:

• Induced pain results from heightened sensitivity to stimulation. This includes allodynia (pain from a normally non-painful stimulus) and hyperalgesia (an exaggerated response to a painful stimulus).
• Spontaneous pain is continuous or paroxysmal and occurs independent of any external stimulus.

CPSP most commonly affects the extremities (hand and foot) and is less frequently seen in proximal regions such as the shoulder and thigh.

Epidemiology

Central post-stroke pain is estimated to affect between 8% and 35% of stroke patients. Most cases begin within the first month post-stroke, though a smaller proportion develop CPSP at 12 months, occasionally extending to between 1 and 6 years post-stroke. . Overall, CPSP most commonly emerges within 1-3 months of stroke onset.. Of stroke survivors who go on to develop CPSP, the large majority had an ischaemic rather than a haemorrhagic stroke (86.1% vs 13.9%). This reflects the relative composition of the CPSP population by stroke type, driven mainly by the higher overall incidence of ischaemic stroke, rather than a higher per patient risk of CPSP following ischaemic stroke specifically.

Aetiology

CPSP arises from damage to the somatosensory structures that carry and process pain signals: the spinothalamic tract, the trigeminothalamic tract, and the thalamus. However, damage to these structures does not always lead to CPSP, and two factors appear to influence risk:

1. Type of stroke. Ischaemic strokes are more likely to cause CPSP than haemorrhagic strokes.
2. Lesion site. Injury to the thalamus and brainstem carries a higher risk of CPSP than damage lower in the spinal cord. Damage to the spinothalamic tract itself appears to carry a greater risk than an isolated thalamic lesion, though the precise mechanism behind this difference is still unclear.

Figure 1. Central Poststroke Pain Syndrome, Potential Sites of Involvement. Lesions at various levels of the spinothalamic tract, including the thalamus, can contribute to central poststroke pain syndrome. Thalamic lesions were initially thought to be solely responsible, but later research identified the involvement of the lateral medulla, pons, lenticulocapsular area, and cortex. The condition may result from the loss of somatosensory integration and changes in cortical plasticity.

Lesion location and extent also help explain the variability in presentation. A lesion at any point along the spinothalamic pathway, not only in the thalamus, can produce a CPSP presentation, and mapping studies increasingly link the specific pattern of somatosensory loss to the location of the underlying lesion.

Pathophysiology

The mechanisms underlying CPSP are not fully understood, and several complementary theories have been proposed:

1. Disinhibition theory: Injury to the lateral thalamus removes cortical inhibitory control over thalamic activity, allowing uncontrolled excitatory output from the thalamus. This thalamic hyperactivity is thought to manifest clinically as CPSP.
2. Spinothalamic pathway damage: Lesions at any level of this pathway can trigger hyperexcitability in the lateral thalamus, which in turn contributes to CPSP.
3. Thalamo-limbic dysregulation: Increased connectivity between the thalamus and amygdala is associated with abnormal activity between the medial thalamus and cingulate cortex. This is mediated by brain-derived neurotrophic factor (BDNF) and involves an imbalance between GABAergic (inhibitory) and glutamatergic (excitatory) signalling, contributing to a pattern of thalamocortical dysrhythmia characteristic of CPSP.
4. Maladaptive neuroplasticity: Cortical and thalamic hyperexcitability following stroke may drive pathological spontaneous pain and hypersensitivity through abnormal changes in brain plasticity.

Clinical Features

Post-stroke pain is a heterogeneous category that includes both nociceptive pain (for example, hemiplegic shoulder pain) and central neuropathic pain (CPSP itself). Distinguishing between subtypes matters clinically, since the two respond to different management approaches, and the pattern of somatosensory loss can help identify which subtype is present.

CPSP itself presents in three main ways:

• Spontaneous pain: burning, pricking, freezing, aching, or squeezing sensations that may occur alone or together, and can be triggered by touch, movement, stress, or cold.
• Evoked pain: pain triggered by nociceptive or non nociceptive stimuli, encompassing hyperalgesia, dysaesthesia, and allodynia.
• Intermittent pain: often described as shooting or lacerating, and a major contributor to reduced quality of life after stroke.

Impact on Function and Quality of Life

CPSP rarely affects pain alone. Persistent neuropathic pain is closely associated with poorer sleep, low mood, and reduced overall quality of life in stroke survivors.

• Pain and sensory disturbance are associated with reduced confidence in moving the affected limb and with avoidance of activity in stroke survivors.
• Reduced activity is associated with deconditioning and further limb disuse. Whether this actively worsens motor recovery specifically because of CPSP has not been directly established in the sources reviewed; this should be read as a plausible clinical concern rather than a proven causal link.
• Physical decline and persistent pain are each independently associated with increased risk of low mood, and low mood is in turn associated with reduced rehabilitation engagement; direct evidence that this specific chain occurs in CPSP is limited, and current support draws mainly from broader post-stroke pain and mood literature.
• Because CPSP is often resistant to pharmacological treatment, this cycle can persist longer than the acute stroke recovery period, making early identification and multidisciplinary input important.

Recognising this cycle supports a rationale for combining physical rehabilitation with psychological support aids overall management, rather than treating pain in isolation from mood and function.

Diagnosis

CPSP is a diagnosis of exclusion: nociceptive, psychogenic, and peripheral neuropathic causes of pain must be ruled out first. A thorough history, clinical examination, and sensory testing should be supplemented with neuroimaging (CT or MRI) to visualise the infarcted or haemorrhagic area of the brain. CPSP is expected to present contralateral to the affected cerebral hemisphere.\

Structured sensory assessment can improve diagnostic confidence. Quantitative sensory testing, combined with a validated pain questionnaire such as the Neuropathic Pain Symptom Inventory, has been shown to help distinguish central neuropathic pain from non-neuropathic post-stroke pain in clinical practice. Where available, these tools are a useful adjunct to bedside examination rather than a replacement for it.

Management

CPSP has no single first-line management pathway, and treatment decisions should be individualised. Current approaches fall into three categories: pharmacological, neuromodulation, and physiotherapy rehabilitation.

Pharmacologic Management

Pharmacological treatment remains the first-line approach and typically follows a three-drug framework: anticonvulsants, antidepressants, and analgesics, each targeting different pain mechanisms.

• Anticonvulsants (for example, pregabalin, gabapentin) modulate neuronal excitability and reduce pain signalling.
• Antidepressants (for example, amitriptyline, duloxetine) act on neurotransmitter systems involved in pain modulation.
• Based on current evidence, amitriptyline, lamotrigine, and gabapentinoids are recommended as first-line pharmacotherapy options when CPSP is suspected, with fluvoxamine, corticosteroids, or intravenous lidocaine/ketamine reserved for intractable cases.

Pharmacological Evidence

A 2024 systematic review and meta-analysis found that pharmacological therapy had a small but statistically significant effect on mean pain score, underlining that even first-line drug treatment offers only partial relief for many patients. This reinforces the case for a multidisciplinary approach rather than pharmacotherapy alone.

Nonpharmacologic Management

Repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation are the most studied non-pharmacological interventions for CPSP. rTMS delivers magnetic impulses through the scalp to modulate nerve signalling, with high frequency stimulation (above 1 Hz) generally more effective than low-frequency protocols. Stimulation targeted at the primary motor cortex (M1) has shown pain reduction in several trials, with functional MRI evidence suggesting pain modulation occurs via corticothalamic and thalamocortical loops rather than the spinothalamic tract alone.

Nonpharmacological Evidence

A 2024 meta-analysis of randomised controlled trials found rTMS produced a measurable reduction in pain intensity for CPSP, though the authors noted the overall quality of the evidence base remains limited and long-term outcomes beyond three months are still underexplored.

A 2025 systematic review and meta-analysis of CPSP management found neuromodulation to have a moderate, statistically significant pooled effect on pain (SMD −0.60, 95% CI −0.97 to −0.23), the only intervention category in that review to reach statistical significance.

Physiotherapy and Rehabilitation

Physiotherapy has a clear role in supporting function, mobility, and quality of life after stroke, and can contribute to mood and overall wellbeing through structured activity and rehabilitative exercise.

Structured therapeutic exercise, graded activity, and task-specific training form the core of general post-stroke rehabilitation and are supported by extensive evidence for improving strength, mobility, and independence after stroke, but this evidence is not specific to CPSP pain reduction. A systematic review of physiotherapy interventions for central neuropathic pain of any underlying cause found significant benefit for exercise and TENS specifically in people with central neuropathic pain due to multiple sclerosis, and for acupuncture specifically in stroke populations, but did not identify equivalent evidence for general therapeutic exercise or graded activity reducing pain intensity in CPSP itself. Aerobic exercise and physical activity therefore remain appropriate for their well-established contribution to general post-stroke recovery, function, mood, and cardiovascular health, but should not be presented to patients as a direct treatment for CPSP pain intensity.

Physiotherapy Evidence

A 2025 systematic review and meta-analysis of central poststroke pain (CPSP) management found limited evidence for physical interventions.[5] Pooled analysis of two small acupuncture trials showed a moderate but statistically non-significant reduction in pain (SMD -0.55, 95% CI -1.28 to 0.18), with high risk of bias and low-to-very-low certainty evidence. Given the small number of trials and participants, this should be read as inconclusive rather than as evidence against physical interventions.

A separate study examining virtual reality (VR), reported narratively within the same review, suggested it may influence pain threshold in stroke patients.

These findings relate specifically to acupuncture and VR. Mirror therapy, graded motor imagery, therapeutic exercise, and sensory retraining were not evaluated in this review, so their effectiveness for CPSP remains unestablished rather than disproven. Further high-quality controlled trials are needed to clarify the role of physical interventions in CPSP management.

Clinical Guidelines and Evidence Gaps

There is currently no single internationally endorsed clinical guideline specific to CPSP. Recommendations are instead drawn from a small number of systematic reviews and expert narrative reviews, several of which explicitly call for larger, better-designed randomised controlled trials across all three management categories above. Clinicians should treat CPSP management as an individualised, multidisciplinary process rather than a fixed treatment algorithm, reassessing regularly against the patient's pain, function, and mood.

Conclusion

CPSP is an under-recognised but relatively common consequence of stroke, affecting more than 1 in 10 survivors and often persisting well beyond the acute recovery period. It is a diagnosis of exclusion built on history, sensory examination, and neuroimaging, and its impact extends beyond pain itself into mood, sleep, and physical function. Current management combines pharmacological treatment, neuromodulation, and physiotherapy-led rehabilitation, but the evidence base for each, particularly for physical interventions, remains limited, and evidence for specific adjuncts such as mirror therapy and graded motor imagery in CPSP is currently limited to case-report level or extrapolated from other pain conditions such as complex regional pain syndrome, and no CPSP-specific clinical guideline yet exists. For physiotherapists, the most defensible role is in supporting function, activity, and quality of life within a wider multidisciplinary pain management plan, while communicating honestly with patients about what physical rehabilitation can and cannot be expected to achieve for pain itself.