Central Post-Stroke Pain

Central post-stroke pain (CPSP) is a type of chronic neuropathic pain that arises following a stroke affecting the central nervous system. Unlike ordinary aches or musculoskeletal discomfort, CPSP originates from damage to pain-processing pathways in the brain, leading to abnormal pain signals even when no harmful stimulus is present. Patients often describe CPSP as burning, shooting, or electric-shock sensations, and it can severely impair daily function and quality of life. The onset may be immediate or delayed by weeks to months after the stroke event, and the pain tends to be persistent and difficult to treat with conventional analgesics.

Central post-stroke pain (CPSP) is a chronic neuropathic pain syndrome arising after a cerebrovascular accident. It typically manifests in the body region corresponding to the injured brain area, most often following thalamic strokes but also seen with lesions along the spinothalamic pathways pubmed.ncbi.nlm.nih.govaapmr.org. Patients experience a paradoxical combination of numbness and hypersensitivity—sensory loss alongside burning, stabbing, or shooting pain—due to deafferentation and maladaptive neuronal hyperexcitability within central nociceptive pathways pubmed.ncbi.nlm.nih.govahajournals.org. Onset usually occurs within weeks to months of the stroke, though delayed presentations beyond six months have been reported aapmr.org.

Types of Central Post-Stroke Pain

Thalamic CPSP
Thalamic CPSP occurs when the stroke injures the ventral posterolateral or ventral posteromedial nuclei of the thalamus. Because these nuclei relay sensory information from the body to the cortex, their damage can produce intense, intractable pain on the opposite side of the body. Patients may experience continuous burning or squeezing pain, often with exaggerated responses to touch or temperature changes.

Extratalamic CPSP
When lesions affect structures outside the thalamus—such as the internal capsule, brainstem, or cortex—it is termed extrathalamic CPSP. The pain distribution and quality may vary widely according to lesion location; for example, brainstem strokes can cause facial pain, while cortical strokes may lead to pain localized to limbs.

Delayed-Onset CPSP
Some patients develop CPSP weeks or even months after their stroke, in what is called delayed-onset CPSP. This phenomenon reflects maladaptive brain plasticity: over time, injured neurons and supporting cells reorganize in ways that amplify pain signals. Recognition of this type is crucial, as patients and clinicians may not immediately link the pain to prior stroke.

Acute-Onset CPSP
In contrast, acute-onset CPSP begins within days of the stroke. Rapid development suggests that the initial injury triggers immediate hypersensitivity in surviving pain pathways. Early-onset CPSP can be severe, and prompt intervention may help reduce central sensitization.

Causes of Central Post-Stroke Pain

1. Thalamic Infarction
   A stroke in the thalamus disrupts the primary relay center for sensory signals, causing abnormal processing of pain information. Loss of inhibitory control here leads to unchecked pain signaling and chronic discomfort.

2. Pontine Lesions
   Infarcts in the pons can damage spinothalamic tracts, which carry pain and temperature signals. Interruption of these tracts causes the brain to misinterpret input from the body, resulting in pain without a peripheral trigger.

3. Cortical Infarction
   Damage to sensory cortex areas can alter how pain stimuli are perceived and interpreted. Patients may develop hypersensitivity to normal sensations or spontaneous pain originating purely from cortical dysfunction.

4. Hemorrhagic Stroke
   Bleeding into brain tissue triggers inflammation, disrupting central pain pathways similarly to ischemic injury. The combination of mechanical damage and inflammatory cascades heightens the risk of CPSP.

5. Lacunar Infarcts
   Small vessel strokes in deep brain structures can injure discrete pain-processing pathways. Even tiny lesions in strategic locations may lead to severe, localized central pain.

6. Neuroinflammation
   After stroke, activated microglia and astrocytes release cytokines that sensitize neurons in pain circuits. Chronic neuroinflammation perpetuates pain by lowering the threshold for pain signal transmission.

7. Demyelination
   Loss of myelin around pain-carrying fibers slows or alters signal conduction. Errant signaling along demyelinated tracts can be perceived as pain, even without external stimuli.

8. Maladaptive Plasticity
   The brain’s attempt to rewire after injury sometimes reinforces painful connections. Such maladaptive changes strengthen excitatory pathways, making pain sensations more intense and persistent.

9. Disruption of Inhibitory Pathways
   GABAergic and glycinergic interneurons normally dampen pain signals. If stroke damages these inhibitory circuits, excitatory neurons fire unchecked, causing hyperalgesia.

10. Central Sensitization
    Repeated or intense stimulation of central neurons leads them to become hyper-responsive. Once sensitized, even mild inputs can provoke disproportionate pain.

11. Oxidative Stress
    Excess free radicals generated during ischemia-reperfusion injure neurons in pain pathways. Oxidative damage can result in spontaneous firing of pain-transmitting neurons.

12. Blood–Brain Barrier Disruption
    Stroke can compromise the blood–brain barrier, allowing inflammatory cells and molecules to infiltrate the brain. This infiltration can irritate central pain pathways and sustain neuropathic pain.

13. Secondary Neuronal Death
    Ongoing cell loss in regions adjacent to the initial stroke enlarges the area of damaged pain-processing tissue. As more neurons die, pain control networks weaken further.

14. Microglial Activation
    Triggered by brain injury, microglia release pro-inflammatory mediators that sensitize nearby neurons. Persistent microglial activity is implicated in the chronicity of CPSP.

15. Astrocyte Proliferation
    Reactive astrocytes form glial scars that alter neuronal connectivity. These scars can disrupt normal pain modulation and perpetuate neuropathic pain states.

16. Serotonergic Dysregulation
    Stroke may affect brainstem nuclei that produce serotonin, a key modulator of pain. Reduced serotonin tone can diminish descending pain inhibition, contributing to CPSP.

17. Noradrenergic Imbalance
    Similar to serotonin, noradrenaline from the locus coeruleus helps suppress pain signals. Damage to noradrenergic pathways removes this protective brake.

18. Genetic Susceptibility
    Variations in genes related to inflammatory responses or ion channels may predispose some stroke survivors to develop CPSP. Genetic factors can influence both onset risk and severity.

19. Comorbid Diabetes
    High blood sugar levels exacerbate nerve damage and inflammation. Diabetic patients may experience worse or earlier CPSP due to pre-existing neuropathic vulnerabilities.

20. Depression and Anxiety
    Psychological factors can lower pain thresholds and amplify perceived intensity. Emotional stress interacts with central pathways to worsen chronic pain after stroke.

Symptoms of Central Post-Stroke Pain

1. Burning Sensation
   A constant, deep warmth or fire-like feeling in affected limbs that persists without any heat source.

2. Shooting Pain
   Abrupt, electric-shock–like jolts that travel along the body, often triggered by movement or light touch.

3. Stabbing Pain
   Sharp, knife-like pains that come on suddenly and may last seconds to minutes before subsiding.

4. Dysesthesia
   Unpleasant abnormal sensations, such as pins and needles or crawling sensations under the skin.

5. Allodynia
   Pain elicited by normally non-painful stimuli, like a soft touch or gentle breeze against the skin.

6. Hyperalgesia
   Exaggerated pain response to mildly painful stimuli, such as a light pinprick feeling excruciating.

7. Spontaneous Pain
   Pain that arises without any external trigger, often described as persistent and unpredictable.

8. Cold Hyperalgesia
   Intense pain brought on by mild cold exposure, such as touching cool objects or drafty air.

9. Thermal Allodynia
   Pain in response to normally non-painful temperature changes, like lukewarm water feeling burning.

10. Mechanical Allodynia
    Pain caused by gentle pressure or movement against the skin, such as clothing brushing.

11. Continuous Ache
    A dull, ongoing soreness that may fluctuate in intensity but never fully disappears.

12. Intermittent Throbbing
    Rhythmic pulsations of pain that often align with the patient’s heartbeat or movement.

13. Electric Shock-Like Jabs
    Sudden, transient bursts of severe pain resembling small electrical discharges under the skin.

14. Deep Aching
    Pain felt deep within muscles or joints, often difficult to pinpoint but persistently troubling.

15. Surface Pain
    Pain localized to the skin or just beneath it, making light touches feel distressing.

16. Tingling (Paresthesia)
    “Pins and needles” sensations that may precede or accompany other pain types.

17. Numbness with Pain
    Paradoxical combination of reduced sensation (numbness) alongside painful feelings in the same area.

18. Pricking Pain
    Sensations similar to tiny needles repeatedly poking the skin.

19. Itchy Pain
    An unusual blend of itching and burning that can feel both irritating and painful.

20. Emotional Distress
    Anxiety, irritability, or depression arising from chronic pain, which in turn can heighten pain perception.

Diagnostic Tests

Physical Exam Tests

1. Sensory Mapping
   A systematic assessment of touch, temperature, and pain threshold across limbs to pinpoint areas of altered sensation.

2. Light Touch Assessment
   Using a cotton wisp to stroke the skin gently and noting areas where touch is perceived as painful or absent.

3. Pinprick Test
   Applying a sterile pin to test nociceptive (pain) pathways; exaggerated or absent responses indicate neuropathy.

4. Temperature Discrimination
   Using metal objects of known temperatures to test cold and warm sensation differences on each side of the body.

5. Vibration Sense
   A 128-Hz tuning fork placed on bony prominences tests large-fiber pathways; reduced vibration indicates central dysfunction.

6. Proprioception Testing
   Moving a joint (e.g., the big toe) up or down with eyes closed to assess position sense and central integration.

7. Muscle Strength Assessment
   Manual resistance applied to key muscle groups; weakness may accompany central lesions contributing to abnormal pain.

8. Reflex Testing
   Evaluating deep tendon reflexes with a reflex hammer; hyperreflexia can accompany central lesions that also cause CPSP.

9. Gait Observation
   Watching the patient walk for signs of antalgic gait, asymmetry, or stiffness related to pain avoidance.

10. Posture Analysis
    Examining standing and sitting positions for protective postures adopted to minimize pain.

Manual Tests

11. Von Frey Filament Testing
    Application of calibrated monofilaments to quantify mechanical pain thresholds and detect allodynia.

12. Brush Allodynia Test
    Light brushing of the skin with a soft brush to assess if non-painful stimuli provoke pain.

13. Two-Point Discrimination
    Gently touching the skin with two points at varying distances to evaluate sensory acuity and central processing.

14. Pressure Pain Threshold
    Gradually increasing pressure with a handheld algometer until pain is reported, measuring sensitivity.

15. Thermal Grill Illusion
    Alternating warm and cool stimuli to evoke paradoxical pain sensations, indicating central sensitization.

16. Wind-Up Ratio
    Delivering repeated pinpricks at the same spot to assess temporal summation of pain, a marker of central sensitization.

17. Pinwheel (Wartenberg Wheel)
    Rolling a spiked wheel over the skin to evaluate mechanosensitivity and allodynia.

18. Dynamic Mechanical Allodynia
    Rubbing the skin with a soft tool to assess pain from moving touch.

Lab and Pathological Tests

19. Complete Blood Count (CBC)
    Identifies systemic inflammation or infection that may influence neuropathic pain severity.

20. Erythrocyte Sedimentation Rate (ESR)
    Elevated rates suggest ongoing inflammation potentially exacerbating central sensitization.

21. C-Reactive Protein (CRP)
    A marker of acute inflammation that may correlate with inflammatory contributions to CPSP.

22. Blood Glucose and HbA1c
    Screening for diabetes, as hyperglycemia worsens neuropathic pain and central sensitization.

23. Lipid Profile
    Detects dyslipidemia, a stroke risk factor that also influences vascular health and secondary inflammation.

24. Vitamin B12 Level
    Deficiency can cause neuropathic symptoms that compound central pain after stroke.

25. Cytokine Panel
    Measures pro-inflammatory mediators (e.g., IL-6, TNF-α) that promote central neuron sensitization.

26. Autoimmune Antibody Screen
    Rules out concurrent autoimmune disorders that might present with central pain features.

27. Thyroid Function Tests
    Hypo- or hyperthyroidism can alter pain perception and must be ruled out.

28. Cerebrospinal Fluid (CSF) Analysis
    Evaluates central inflammation or infection when CPSP presents atypically or rapidly worsens.

Electrodiagnostic Tests

29. Nerve Conduction Studies
    Measure speed and amplitude of peripheral nerve signals to distinguish central from peripheral neuropathic pain.

30. Electromyography (EMG)
    Assesses muscle electrical activity; abnormal findings point to peripheral involvement alongside CPSP.

31. Somatosensory Evoked Potentials (SSEPs)
    Record brain responses to peripheral stimulation; delays or abnormalities indicate central pathway disruption.

32. Laser-Evoked Potentials (LEPs)
    Use laser stimuli to selectively activate pain fibers and record cortical responses, pinpointing central processing defects.

33. Quantitative Sensory Testing (QST)
    A battery of standardized tests assessing sensory thresholds across modalities to quantify central sensitization.

34. Blink Reflex Study
    In facial CPSP, tests brainstem circuits by measuring responses to supraorbital nerve stimulation.

35. Thermal Sensory Testing
    Computer-controlled heating and cooling probes map thermal thresholds and allodynia distribution.

Imaging Tests

36. Magnetic Resonance Imaging (MRI)
    High-resolution images reveal the precise location and extent of stroke lesions affecting pain pathways.

37. Functional MRI (fMRI)
    Maps brain activity in response to pain stimuli, showing altered patterns in CPSP patients.

38. Diffusion Tensor Imaging (DTI)
    Visualizes white-matter tract integrity, detecting damage to spinothalamic or thalamocortical fibers.

39. Positron Emission Tomography (PET)
    Measures metabolic activity in pain-processing regions, highlighting areas of hyperactivity or hypometabolism.

40. Single-Photon Emission Computed Tomography (SPECT)
    Evaluates blood flow changes in central pain networks, supporting diagnosis when MRI is inconclusive.

Non-Pharmacological Treatments

A. Physiotherapy & Electrotherapy

1. Transcutaneous Electrical Nerve Stimulation (TENS)
   Description: Delivers low-intensity electrical pulses via skin electrodes.
   Purpose: Modulate pain transmission and provide relief.
   Mechanism: Activates large-fiber afferents, closing the “gate” at the dorsal horn and promoting endogenous opioid release en.wikipedia.orgen.wikipedia.org.

2. Functional Electrical Stimulation (FES)
   Description: Burst electrical currents target motor nerves in affected limbs.
   Purpose: Improve muscle strength, reduce spasticity, and alleviate secondary pain.
   Mechanism: Stimulates muscle contractions, enhancing circulation and remodeling of central sensorimotor circuits en.wikipedia.orgen.wikipedia.org.

3. Mirror Therapy
   Description: Patient performs movements with the unaffected limb while viewing its reflection in a mirror.
   Purpose: Retrain sensorimotor integration and reduce pain in the affected side.
   Mechanism: Provides visual feedback to “trick” the brain into perceiving normal movement, normalizing cortical excitability en.wikipedia.orgfrontiersin.org.

4. Neuromuscular Electrical Stimulation (NMES)
   Description: Low-frequency pulses stimulate peripheral nerves to induce muscle contraction.
   Purpose: Strengthen peri-lesional muscles, improve motor control, and decrease musculoskeletal contributors to CPSP.
   Mechanism: Enhances neuromuscular junction efficacy and promotes neuroplastic changes in motor cortex en.wikipedia.orgen.wikipedia.org.

5. Interferential Current Therapy (IFC)
   Description: Two medium-frequency currents intersect to produce a low-frequency effect deep in tissues.
   Purpose: Deep analgesia and muscle relaxation.
   Mechanism: Similar gate-control effects as TENS but reaching deeper nociceptive fibers en.wikipedia.orgen.wikipedia.org.

6. Ultrasound Therapy
   Description: High-frequency sound waves delivered via a transducer.
   Purpose: Promote tissue healing, reduce inflammation, and modulate pain.
   Mechanism: Mechanical vibratory energy increases local blood flow and disrupts pain-mediating nociceptors en.wikipedia.orgen.wikipedia.org.

7. Low-Level Laser Therapy (LLLT)
   Description: Low-energy lasers target painful tissues.
   Purpose: Alleviate neuropathic pain and speed nerve regeneration.
   Mechanism: Photobiomodulation reduces oxidative stress, promotes mitochondrial ATP production, and downregulates pro-inflammatory cytokines en.wikipedia.orgen.wikipedia.org.

8. Spinal Manipulative Therapy
   Description: Manual adjustment of vertebral segments by a trained therapist.
   Purpose: Relieve discomfort from secondary musculoskeletal pain.
   Mechanism: Alters proprioceptive input to the dorsal horn, modulating nociceptive processing physio-pedia.comen.wikipedia.org.

9. Acupuncture
   Description: Insertion of fine needles at specific meridian points.
   Purpose: Reduce neuropathic pain and improve quality of life.
   Mechanism: Stimulates endogenous opioid release and modulates descending inhibitory pathways en.wikipedia.orgphysio-pedia.com.

10. Vestibular Rehabilitation
    Description: Exercises to enhance balance and vestibular compensation.
    Purpose: Address dizziness or imbalance that can exacerbate pain.
    Mechanism: Promotes neuroplasticity in vestibular nuclei, reducing maladaptive sensory weighting physio-pedia.comen.wikipedia.org.

11. Dynamic Bracing & Splinting
    Description: Custom orthoses support hypertonic or flaccid limbs.
    Purpose: Prevent joint stiffness, reduce secondary musculoskeletal pain.
    Mechanism: Maintains optimal limb positioning, minimizing abnormal sensory input physio-pedia.comen.wikipedia.org.

12. Thermotherapy (Heat Packs)
    Description: Superficial heating via packs or warm baths.
    Purpose: Increase local blood flow and relax soft tissue.
    Mechanism: Vasodilation reduces ischemia, dampens nociceptor firing en.wikipedia.orgen.wikipedia.org.

13. Cryotherapy (Cold Packs)
    Description: Application of cold compresses.
    Purpose: Decrease acute pain and inflammatory mediators.
    Mechanism: Vasoconstriction reduces edema and slows nerve conduction velocity en.wikipedia.orgen.wikipedia.org.

14. Hydrotherapy
    Description: Exercises in warm water pools.
    Purpose: Provide low-impact strengthening and pain relief.
    Mechanism: Buoyancy offloads joints, heat promotes circulation, reducing central sensitization en.wikipedia.orgen.wikipedia.org.

15. Manual Therapy
    Description: Hands-on soft tissue mobilization by therapists.
    Purpose: Improve joint mobility, reduce muscle tension.
    Mechanism: Modulates mechanoreceptors, influencing central pain processing physio-pedia.comen.wikipedia.org.

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B. Exercise Therapies

1. Aerobic Training
   Description: Moderate-intensity walking, cycling, or treadmill.
   Purpose: Enhance cardiovascular fitness and endogenous analgesia.
   Mechanism: Increases endorphin and endocannabinoid levels, reducing central sensitization en.wikipedia.orgen.wikipedia.org.

2. Resistance Training
   Description: Weight or band exercises targeting major muscle groups.
   Purpose: Build strength, correct muscle imbalances contributing to pain.
   Mechanism: Induces muscle hypertrophy and improved motor unit recruitment, normalizing afferent feedback en.wikipedia.orgen.wikipedia.org.

3. Stretching & Flexibility
   Description: Static and dynamic stretching routines.
   Purpose: Reduce muscle tightness and joint stiffness secondary to spasticity.
   Mechanism: Prolonged stretch desensitizes muscle spindles, modulating dorsal horn excitability en.wikipedia.orgen.wikipedia.org.

4. Balance & Proprioception Training
   Description: Tandem stance, single-leg stands, wobble board exercises.
   Purpose: Improve postural control and reduce fall-related pain.
   Mechanism: Enhances integration in cerebellar and proprioceptive pathways, alleviating maladaptive hyperexcitability en.wikipedia.orgen.wikipedia.org.

5. Gait Training
   Description: Treadmill or overground walking with therapist support.
   Purpose: Normalize gait patterns, reduce musculoskeletal strain.
   Mechanism: Re-establishes rhythmic sensorimotor loops, dampening central sensitization en.wikipedia.orgen.wikipedia.org.

6. Tai Chi
   Description: Slow, flowing martial art sequences.
   Purpose: Combine balance, strength, and mindfulness for pain relief.
   Mechanism: Integrates motor planning and cognitive focus, enhancing descending inhibition en.wikipedia.org.

7. Yoga
   Description: Postures (asanas) and breathing exercises (pranayama).
   Purpose: Improve flexibility, breath control, and mental relaxation.
   Mechanism: Lowers cortisol, increases GABAergic tone, reducing pain perception en.wikipedia.org.

8. Pilates
   Description: Core-strength and posture control exercises.
   Purpose: Strengthen trunk muscles, improving support to affected limbs.
   Mechanism: Enhances proprioceptive feedback and spinal stability, modulating nociceptive input en.wikipedia.org.

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C. Mind-Body Therapies

1. Cognitive Behavioral Therapy (CBT)
   Description: Structured sessions targeting pain-related thoughts.
   Purpose: Reframe maladaptive beliefs, reduce catastrophizing.
   Mechanism: Alters prefrontal cortex regulation of pain, enhancing top-down inhibition jpain.orgen.wikipedia.org.

2. Mindfulness Meditation
   Description: Focused attention on breath and body sensations.
   Purpose: Increase present-moment awareness, reduce pain interference.
   Mechanism: Deactivates default mode network, boosts anterior cingulate cortex control over pain en.wikipedia.org.

3. Guided Imagery
   Description: Therapist-led visualization of peaceful scenes.
   Purpose: Distract from pain and induce relaxation.
   Mechanism: Activates prefrontal cortex and periaqueductal gray, enhancing endogenous opioid release en.wikipedia.org.

4. Biofeedback
   Description: Real-time display of physiological signals (e.g., EMG).
   Purpose: Teach patients to self-regulate muscle tension and heart rate.
   Mechanism: Strengthens cortical control over autonomic responses, reducing central hyperexcitability en.wikipedia.org.

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D. Educational Self-Management

1. Pain Education Workshops
   Description: Group sessions on understanding neuropathic pain.
   Purpose: Empower patients with knowledge to self-manage symptoms.
   Mechanism: Reduces fear-avoidance behaviors, normalizes pain signals en.wikipedia.org.

2. Pacing & Activity Planning
   Description: Coaching on graded activity and rest intervals.
   Purpose: Prevent pain flares by avoiding overexertion.
   Mechanism: Modulates sensory thresholds by balancing activity levels en.wikipedia.org.

3. Goal-Setting & Self-Monitoring
   Description: Personalized goal worksheets and pain diaries.
   Purpose: Track progress, maintain motivation, identify triggers.
   Mechanism: Reinforces positive behaviors and enhances prefrontal cortex control of pain perception en.wikipedia.org.

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Pharmacological Treatments

1. Amitriptyline (TCA)
   Dosage: Start 10 mg at bedtime, titrate up to 75 mg/day scielo.brstrokebestpractices.ca.
   Time: Once daily at night.
   Side Effects: Anticholinergic effects (dry mouth, urinary retention), sedation, orthostatic hypotension.

2. Nortriptyline (TCA)
   Dosage: 10–50 mg at bedtime.
   Time: Once daily.
   Side Effects: Lower anticholinergic burden than amitriptyline; possible drowsiness and hypotension uspharmacist.comscielo.br.

3. Gabapentin (Anticonvulsant)
   Dosage: Start 300 mg TID, titrate to 2400 mg/day strokebestpractices.castrokebestpractices.ca.
   Time: Divided doses.
   Side Effects: Dizziness, somnolence, peripheral edema.

4. Pregabalin (Anticonvulsant)
   Dosage: 75–150 mg/day in two divided doses; max 600 mg/day strokebestpractices.ca.
   Time: Morning and evening.
   Side Effects: Weight gain, dizziness, blurred vision.

5. Lamotrigine (Anticonvulsant)
   Dosage: Start 25 mg daily, titrate to 200–400 mg/day uspharmacist.comscielo.br.
   Time: Once daily.
   Side Effects: Rash (Stevens–Johnson syndrome), headache.

6. Carbamazepine (Anticonvulsant)
   Dosage: 100 mg BID, titrate to 600–1200 mg/day.
   Time: Morning and evening.
   Side Effects: Hyponatremia, dizziness, ataxia.

7. Duloxetine (SNRI)
   Dosage: 30 mg once daily, may increase to 60 mg.
   Time: Morning.
   Side Effects: Nausea, dry mouth, insomnia.

8. Venlafaxine (SNRI)
   Dosage: 37.5–75 mg once daily.
   Time: Morning.
   Side Effects: Increased blood pressure, sweating.

9. Tramadol (Weak opioid)
   Dosage: 50–100 mg Q4–6 h PRN; max 400 mg/day.
   Time: PRN for breakthrough pain.
   Side Effects: Nausea, constipation, dependence risk.

10. Tapentadol (Opioid)
    Dosage: 50–100 mg Q4–6 h PRN; max 600 mg/day.
    Time: PRN.
    Side Effects: Similar to tramadol, with less nausea.

11. Ketamine (Low-dose IV)
    Dosage: 0.1–0.5 mg/kg IV over 30 min.
    Time: Infusion sessions.
    Side Effects: Psychotomimetic effects, hypertension mdpi.com.

12. Lidocaine (IV infusion)
    Dosage: 1–5 mg/kg IV over 1–4 h.
    Time: Session-based.
    Side Effects: Arrhythmias, lightheadedness mdpi.com.

13. Mexiletine (Oral sodium-channel blocker)
    Dosage: 150 mg TID.
    Time: Divided.
    Side Effects: GI upset, tremor.

14. Capsaicin (8% patch)
    Dosage: Single application to painful area every 3 months.
    Time: In-clinic application.
    Side Effects: Local burning, erythema.

15. Clonidine (Topical patch)
    Dosage: 0.1–0.3 mg/day patch.
    Time: Weekly patch change.
    Side Effects: Hypotension, sedation.

16. Flupirtine (NMDA modulator; not available in US)
    Dosage: 100 mg TID.
    Time: Divided.
    Side Effects: Hepatotoxicity.

17. Dextromethorphan-quinidine
    Dosage: 20 mg/10 mg BID.
    Time: Morning and evening.
    Side Effects: QT prolongation, dizziness.

18. Cannabinoids (e.g., nabiximols)
    Dosage: 2.7 mg THC/2.5 mg CBD per spray; 1–3 sprays BID.
    Time: Morning and evening.
    Side Effects: Dizziness, dry mouth.

19. Prednisone (Short course)
    Dosage: 20–40 mg daily for 5–7 days.
    Time: Single morning dose.
    Side Effects: Hyperglycemia, mood changes pmc.ncbi.nlm.nih.gov.

20. Pamidronate (Bisphosphonate)
    Dosage: 30–60 mg IV infusion monthly.
    Time: Monthly infusion.
    Side Effects: Fever, hypocalcemia pmc.ncbi.nlm.nih.gov.

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 Dietary Molecular Supplements

1. Alpha-Lipoic Acid
   Dosage: 600 mg/day orally.
   Function: Antioxidant, mitochondrial cofactor.
   Mechanism: Scavenges free radicals, regenerates other antioxidants en.wikipedia.org.

2. Benfotiamine (Vitamin B1 Prodrug)
   Dosage: 300 mg/day.
   Function: Supports nerve metabolism.
   Mechanism: Increases transketolase activity, reducing advanced glycation end products en.wikipedia.org.

3. Methylcobalamin (Vitamin B12)
   Dosage: 500–1500 µg/day.
   Function: Nerve regeneration.
   Mechanism: Promotes myelin repair and methylation reactions en.wikipedia.org.

4. Folate (Vitamin B9)
   Dosage: 400 µg/day.
   Function: Homocysteine reduction.
   Mechanism:** Cofactor in remethylation of homocysteine, reducing neurotoxicity en.wikipedia.org.

5. N-Acetylcysteine (NAC)
   Dosage: 600 mg BID.
   Function: Precursor to glutathione.
   Mechanism: Replenishes intracellular glutathione, reducing oxidative stress en.wikipedia.org.

6. Coenzyme Q10
   Dosage: 100–200 mg/day.
   Function: Mitochondrial support.
   Mechanism: Electron carrier in respiratory chain, antioxidant en.wikipedia.org.

7. Magnesium
   Dosage: 300–400 mg/day.
   Function: NMDA receptor modulation.
   Mechanism: Blocks NMDA channels, reducing excitotoxicity en.wikipedia.org.

8. Omega-3 Fatty Acids
   Dosage: 1–2 g/day EPA/DHA.
   Function: Anti-inflammatory.
   Mechanism:** Inhibits pro-inflammatory eicosanoids, promotes neuroprotectin synthesis en.wikipedia.org.

9. Curcumin
   Dosage: 500 mg BID (with piperine).
   Function: Anti-inflammatory antioxidant.
   Mechanism:** Downregulates NF-κB and COX-2, reducing cytokine release en.wikipedia.org.

10. Vitamin D3
    Dosage: 1000–2000 IU/day.
    Function: Neuroimmune modulation.
    Mechanism:** Regulates inflammatory cytokines, supports neuronal survival en.wikipedia.org.

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Advanced/Regenerative Agents

1. Pamidronate (Bisphosphonate)
   Dosage & Mechanism: See above pmc.ncbi.nlm.nih.gov.

2. Zoledronic Acid
   Dosage: 5 mg IV annually.
   Function: Inhibits microglial activation.
   Mechanism:** Suppresses neuroinflammation pmc.ncbi.nlm.nih.gov.

3. Mesenchymal Stem Cell (MSC) Infusion
   Dosage: 1–2×10^6 cells/kg IV.
   Function: Paracrine neurotrophic support.
   Mechanism:** Releases growth factors (BDNF, NGF) to promote neuronal repair mdpi.com.

4. Neural Progenitor Cell Transplantation
   Dosage: 1×10^6 cells into peri-infarct zone.
   Function: Replace lost neural circuits.
   Mechanism:** Integrates into host tissue, restoring pathways mdpi.com.

5. Platelet-Rich Plasma (PRP)
   Dosage: 3–5 mL injection per site monthly.
   Function: Growth factor delivery.
   Mechanism:** Releases PDGF, TGF-β to enhance synaptic plasticity mdpi.com.

6. Intrathecal IGF-1
   Dosage: Experimental.
   Mechanism:** Promotes myelin repair and neuronal survival mdpi.com.

7. Chondroitinase ABC
   Dosage: Experimental spinal delivery.
   Mechanism:** Degrades inhibitory CSPGs, fostering axonal regrowth mdpi.com.

8. Hyaluronic Acid (Viscosupplementation)
   Dosage: 2 mL intrathecal injection.
   Function: Reduce glial scarring.
   Mechanism:** Modulates extracellular matrix, supporting plasticity mdpi.com.

9. Erythropoietin (EPO)
   Dosage: 30,000 IU IV weekly.
   Function: Neuroprotection.
   Mechanism:** Anti-apoptotic and anti-inflammatory effects mdpi.com.

10. Growth Hormone
    Dosage: 0.1–0.3 mg/kg/day SC.
    Function: Neurotrophic support.
    Mechanism:** Stimulates IGF-1 release, promoting neurogenesis mdpi.com.

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Surgical & Neuromodulation Interventions

1. Motor Cortex Stimulation (MCS)
   Procedure: Epidural electrodes over precentral gyrus.
   Benefits: Modulates cortical excitability, reducing central pain en.wikipedia.orgthelancet.com.

2. Deep Brain Stimulation (DBS) of Thalamic Nuclei
   Procedure: Implanted electrodes in ventral posterolateral thalamus.
   Benefits: Disrupts hyperactive thalamic circuits thelancet.comjpain.org.

3. Spinal Cord Stimulation (SCS)
   Procedure: Epidural leads deliver low-level currents to dorsal columns.
   Benefits: Provides paresthesia that masks central pain en.wikipedia.orgthelancet.com.

4. Dorsal Root Entry Zone (DREZ) Lesioning
   Procedure: Lesion micro-zones in dorsal horn.
   Benefits: Interrupts pathological nociceptive transmission thelancet.comjpain.org.

5. Thalamotomy
   Procedure: Lesion ventral posterolateral nucleus via radiofrequency.
   Benefits: Alleviates thalamic hyperexcitability thelancet.comjpain.org.

6. Cordotomy
   Procedure: Lesion spinothalamic tract in cervical cord.
   Benefits: Blocks ascending pain signals for unilateral pain thelancet.comjpain.org.

7. Gamma Knife Thalamotomy
   Procedure: Focused radiation to thalamic nucleus.
   Benefits: Non-invasive lesioning, pain reduction jpain.org.

8. Selective Posterior Rhizotomy
   Procedure: Sever selected dorsal roots.
   Benefits: Reduces spasticity-related pain en.wikipedia.orgthelancet.com.

9. Intrathecal Drug Pump Implant
   Procedure: Catheter delivers drugs (e.g., baclofen) directly to CSF.
   Benefits: Lower systemic side effects, targeted analgesia en.wikipedia.orgthelancet.com.

10. Cord Electrical Stimulation (CES)
    Procedure: Percutaneous scalp electrodes deliver micro-currents.
    Benefits: Non-invasive neuromodulation reducing central sensitization jpain.org.

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Prevention Strategies

1. Acute Stroke Management: Rapid reperfusion (thrombolysis/thrombectomy) minimizes lesion size en.wikipedia.orgahajournals.org.

2. Secondary Stroke Prevention: Antiplatelet/anticoagulation and risk factor control reduce recurrent injury en.wikipedia.orgahajournals.org.

3. Early Rehabilitation: Initiate physio within 48 h to prevent maladaptive central sensitization en.wikipedia.orgaapmr.org.

4. Pain Education: Inform patients about normal sensory changes to reduce catastrophizing en.wikipedia.org.

5. Glycemic & BP Control: Maintain optimal levels to protect neural microvasculature en.wikipedia.orgahajournals.org.

6. Avoid Neurotoxins: Limit alcohol, nicotine to reduce central sensitization en.wikipedia.org.

7. Maintain Mobility: Prevent secondary musculoskeletal complications en.wikipedia.orgaapmr.org.

8. Vitamin D Supplementation: Supports neural health en.wikipedia.org.

9. Regular Pain Screening: Early identification of CPSP risk aapmr.orgjpain.org.

10. Stress Management: Mind–body techniques to prevent central sensitization en.wikipedia.org.

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When to See a Doctor

• Persistent Pain beyond 4–6 weeks post-stroke.

• Allodynia or Hyperalgesia interfering with daily function.

• Rapidly Worsening Pain or new neurological deficits.

• Uncontrolled Sleep Disturbance due to pain.

• Significant Mood Changes (depression, anxiety).

• Medication Side Effects impairing safety.

• Signs of Secondary Complications (e.g., spasticity, contractures).

• Infection or Skin Breakdown under electrodes/patches.

• Poor Rehabilitation Progress due to pain.

• Questionable Diagnosis warranting further evaluation aapmr.orgjpain.org.

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“Do” & “Avoid” Recommendations

Do

1. Maintain Gentle Activity

2. Use Heat/Cold Responsibly

3. Practice Relaxation Daily

4. Keep a Pain Diary

5. Adhere to Medications

6. Engage in CBT or Counseling

7. Attend All Rehab Sessions

8. Monitor for Side Effects

9. Adopt Healthy Diet

10. Educate Family & Caregivers

Avoid

1. Prolonged Bed Rest

2. Heavy Lifting or Jerky Movements

3. Excessive Caffeine or Alcohol

4. Smoking & Nicotine

5. Overuse of Opioids Without Review

6. Ignoring Mood Changes

7. Self-Medicating with Illicit Drugs

8. Skipping Follow-Ups

9. High-Voltage Electrotherapy Without Supervision

10. Unsupervised High-Intensity Exercise

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Frequently Asked Questions

1. What causes central post-stroke pain?
   Damage to central sensory pathways leads to deafferentation and hyperexcitable neurons pubmed.ncbi.nlm.nih.govahajournals.org.

2. How soon after a stroke does CPSP appear?
   Usually 1–3 months post-stroke, though it can occur immediately or after 6 months aapmr.orgsvn.bmj.com.

3. Is CPSP the same as shoulder pain after stroke?
   No—shoulder pain is often musculoskeletal; CPSP is neuropathic verywellhealth.compubmed.ncbi.nlm.nih.gov.

4. Can CPSP be cured?
   There’s no definitive cure, but multimodal treatments can achieve significant relief jpain.orgstrokebestpractices.ca.

5. Are opioids effective?
   They may help some patients but carry high risk of side effects and dependence jpain.orgstrokebestpractices.ca.

6. What’s the first-line drug?
   Amitriptyline is often first-line, though tolerability limits dosing pubmed.ncbi.nlm.nih.govscielo.br.

7. Are supplements helpful?
   Agents like alpha-lipoic acid and B vitamins can support nerve health but rarely suffice alone en.wikipedia.org.

8. How long do I need therapy?
   Many need ongoing combined therapies; re-assessment every 3–6 months is typical aapmr.org.

9. Does diet matter?
   Anti-inflammatory diets and specific supplements (omega-3, antioxidants) can modulate neuroinflammation en.wikipedia.org.

10. Is surgery common?
    Only considered when refractory to medical/neurostimulation approaches thelancet.comjpain.org.

11. Can children get CPSP?
    Rare but possible; pediatric dosing and therapies differ significantly pubmed.ncbi.nlm.nih.govaapmr.org.

12. Will physical therapy worsen pain?
    Properly dosed, PT usually reduces pain—overexertion can aggravate it en.wikipedia.orgphysio-pedia.com.

13. Is CBT covered by insurance?
    Coverage varies by region; many stroke rehab programs include it jpain.org.

14. Are there novel treatments?
    Stem cell and gene therapies are investigational but show promise mdpi.com.

15. How do I find a CPSP specialist?
    Seek a multidisciplinary pain clinic with experience in central neuropathic pain aapmr.orgjpain.org.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: June 23, 2025.

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