CENTRAL POSTSTROKE PAIN

Author(s): Anthony Pellicane, MD

Originally published:11/10/2011
Last updated:09/17/2015

1. DISEASE/DISORDER:

Definition

Central poststroke pain (CPSP) is a central neuropathic pain syndrome that can occur after stroke in the part of
the body corresponding to the cerebrovascular lesion. CPSP is characterized by pain and sensory abnormalities
localized to the affected area; and, a diagnosis can be made only after having ruled out other potential causes
of nociceptive, psychogenic, or peripheral neuropathic pain.1

Etiology

See Definition and Pathoanatomy/Pathophysiology sections.

Epidemiology including risk factors and primary prevention

1. CPSP develops in 8% of stroke patients.2

2. Most cases present within the first 6 months after stroke (with the majority of cases developing within the
first month). Though rare, it is possible for CPSP to develop immediately after stroke; or, more than 6
months after stroke. 2,4
3. There is no intervention proven to alter the development of CPSP.

Pathoanatomy/Pathophysiology

CPSP is believed to occur after a lesion at any level of the somatosensory pathway of the brain (cerebral
cortex, thalamus, medulla, spinothalamic pathways, thalamocortical pathways) with resultant maladaptive
neuroplastic changes within the central nervous system causing aberrant sensory perception.1,3 Potential causes
of CPSP include:1

1. Central sensitization resulting from increased neuronal excitability of central nociceptive neurons.
2. Disinhibition of pain-signaling structures resulting from damage to inhibitory structures.
3. Thalamic dysfunction resulting from direct thalamic injury or thalamic deafferentation.
4. Derangement of an oscillatory pattern inside a sensory corticothalamocortical reverbatory loop causing the
experience of pain (dynamic reverberation theory).

CPSP likely has multiple potential pathophysiological causes.

Disease progression including natural history, disease phases or stages, disease trajectory
(clinical features and presentation over time)

No prospective, longitudinal studies have documented the clinical course of CPSP; however, it is considered a
potentially life-long complication that is burdensome to the patient and leads to decreased quality of life and
interference with rehabilitation.1

Specific secondary or associated conditions and complications

While no specific conditions and complications secondary to CPSP have been identified, it may restrict a
patient’s ability to participate in rehabilitation programs, thus leading to worsening of spasticity, development
of contracture, and functional limitations.

2. ESSENTIALS OF ASSESSMENT

History

CPSP is a diagnosis of exclusion, thus, careful elimination of other potential causes of pain after stroke must
occur prior to diagnosing CPSP. These potential causes include (but are not limited to) complex regional pain
syndrome, radiculopathy, plexopathy, peripheral mononeuropathy, hemiparetic shoulder pain (impingement
syndrome, rotator cuff injury, adhesive capsulitis, bursitis, painful spasticity, shoulder subluxation), and deep
venous thrombosis. Keys to CPSP symptomatology include:1-5

1. Pain is localized to the area affected by the lesion. Larger body areas are affected more commonly than
smaller body areas.
2. Pain is characterized most often as burning or aching; however, pricking, lacerating, shooting, squeezing,
throbbing, heaviness are all possible qualitative descriptors.
3. Gradual onset is more common.
4. Pain can be spontaneous or evoked (with spontaneous symptoms occurring continuously and/or
paroxysmally and evoked symptoms resulting from nociceptive and/or nonnociceptive stimuli).
5. Symptoms may be aggravated by movement, touch, temperature (cold > warm), emotional stress; and, may
be palliated by movement, temperature (warm), rest, distraction. Note that movement and warmth (for
example) may aggravate or palliate symptoms.
6. It is generally accepted that there are no pain features pathognomonic for or universally present in CPSP.

Physical examination

There are no uniform signs associated with CPSP. Negative and positive sensory events are characteristic of
CPSP.1,3

1. Negative sensory events including decreased sensation to thermal (particularly cold) and pain (pinprick)
stimuli within the painful area are common in CPSP. Less common negative sensory events include
decreased sensation to light touch and changes in joint position.
2. Positive sensory events including hyperalgesia to pain (pinprick) and allodynia to light touch and thermal
stimuli (particularly cold) are common in CPSP. Less common positive sensory events include
aftersensations, radiation of pain, and summation.

Laboratory studies

No laboratory studies are currently used for the assessment of CPSP.

Imaging

Identification of a central lesion with MRI or CT that corresponds to the painful body area is an important and
appropriate component in the diagnosis of CPSP.

Supplemental assessment tools

Pain drawings, pain scales, and other pain assessment tools are appropriate for the initial assessment of CPSP
and also are useful to monitor the efficacy of interventions.

3. REHABILITATION MANAGEMENT AND TREATMENTS

Available or current treatment guidelines

The treatment of CPSP is challenging and must incorporate pharmacologic and non-pharmacologic
interventions in order to maximize potential for success. Generally speaking, treatment benefits only a fraction
 of patients diagnosed with CPSP; and, response to treatment is incomplete for those whose symptoms do
improve. Goals of treatment, then, should be focused on reduction, not elimination, of symptoms and return to
functional activity. Treatment algorithms typically follow a trial-and-error approach and the concomitant use
of various treatments in one patient is common.

Pharmacologic Management:1,3,5,6 Various antidepressants, anticonvulsants, opioids, N-methyl-D-aspartate

(NMDA) antagonists, antiarrythmics, and gamma-aminobutyric acid (GABA) agonists have been assessed for
efficacy in the treatment of CPSP. An attempt at organizing the various pharmacologic options with regard to
efficacy has been made to help the provider.

1. Antidepressants: Amitriptyline (1st line) and fluvoxamine (3rdline) are considered to be beneficial in the
treatment of CPSP, whereas citalopram and reboxetine are considered ineffective. Fluvoxamine may be
particularly useful in the CPSP patient with concomitant depression.
2. Anticonvulsants: Lamotrigine (1st line) and pregabalin (2ndline) have proven useful in the treatment of
CPSP, whereas gabapentin (2nd line) may be effective in the treatment of
CPSP. Carbamazepine, phenytoin, zonisamide may possess some efficacy
while topiramate and levetiracetam are likely ineffective.
3. Opioids: Tramadol, morphine, and levorphanol (all 3rd line) may be useful in the treatment of CPSP. If
opiods are selected as a treatment option, the aforementioned opiods medications in addition
to tapentadol, methadone, buprenorphine, and oxycodone should be used
preferentially. Naloxone (opioid antagonist) is considered ineffective in the treatment of CPSP.
4. NMDA antagonists: Ketamine may possess some efficacy, however, side effects and administration route
limit its utility. Dextromethorphan is considered ineffective in the treatment of CPSP.
5. Antiarrythmics: Mexiletine and lidocaine (both 3rd line) may be useful in the treatment of CPSP. Their
utility is limited, however, given poor patient tolerance and need for intravenous administration,
respectively.
6. GABA agonists: Intrathecal baclofen possibly has a role in the treatment of CPSP with oral baclofenlikely
not being useful. Propofol and thiamylal/thiopental also possibly have roles in the treatment of CPSP,
however, only in the short-term relief of intractable pain.

Nonpharmacologic Management:1,3,5,6,7 A number of nonpharmacologic interventions have been assessed for

efficacy in the treatment of CPSP. Psychological treatment (for example, relaxation techniques and
biofeedback), exercise therapy, and desensitization techniques may be beneficial in CPSP. Transcutaneous
electrical nerve stimulation (TENS) is likely not effective and may actually increase pain symptoms in some
patients. Repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS),
and vestibular caloric stimulation have demonstrated efficacy in the treatment of CPSP. Deep brain stimulation
(DBS) and motor cortex stimulation via implanted stimulators show variable efficacy and should be reserved
for patients with significant symptomatology who have exhausted pharmacological and less invasive
nonpharmacologic treatment strategies.

Patient & family education

The patient and family should be educated on the unclear etiology of CPSP, its likely chronic duration, the
trial-and-error algorithm typically used for treatment, and the goals of treatment (reduction, not elimination, of
symptoms and return to functional activity). Family training/involvement in nonpharmacologic interventions
(for example, psychological treatments, desensitization techniques) may be beneficial.

Translation into practice: practice “pearls”/performance improvement in practice

(PIPs)/changes in clinical practice behaviors and skills

Interdisciplinary management of CPSP is most appropriate, with goals focused on reducing symptoms and
improving function. Initial management includes medication management (amitriptyline and/or lamotrigine
with tramadol as needed for breakthrough symptoms) coupled with desensitization technique training and
relaxation and/or biofeedback training. Frequent reassessment with adjustment of pharmacological and
nonpharmacological interventions affords patients the best opportunity to reduce symptoms and improve
function.

4. CUTTING EDGE/EMERGING AND UNIQUE CONCEPTS AND

PRACTICE

Cutting edge concepts and practice

Complex regional pain syndrome (CRPS) is another poorly understood painful condition that presents with
allodynia and hyperalgesia. CRPS, however, also possesses additional signs and symptoms including motor,
sudomotor, vasomotor, and trophic abnormalities. CRPS after stroke and CPSP are considered distinct entities;
however, the possibility of these two diagnoses existing on a continuum is not unreasonable.
Pharmacologically, CRPS is treated similarly to CPSP, suggesting the possibility of similar pathophysiology.
Demonstratively, one study reported resolution of symptoms in 91.2% patients with CRPS after stroke using
an oral methylprednisolone taper,8 while another demonstrated significant improvements in patients with CPSP
also receiving an oral methylprednisolone taper.9
 The serotonin-norepinephrine reuptake inhibitors (SNRIs) and methadone have proven efficacy in other
instances of neuropathic pain10 and may be reasonable options for the treatment of CPSP. Additionally, given
its overlap in mechanism of action with tramadol, tapentadol may also be a reasonable option for as needed
pain relief in patients with CPSP. Finally, as alluded to above, exploring oral corticosteroid administration as
an abortive treatment in CPSP might be a worthwhile endeavor as well.

5. GAPS IN THE EVIDENCE-BASED KNOWLEDGE

Gaps in the evidence-based knowledge

The establishment of a universally accepted definition of and diagnostic criteria for CPSP is of paramount
importance both clinically and for research purposes. Consensus on these items as well as consensus on
treatment algorithms should be the focus of national committees. Proposals for diagnostic criteria exist by Klit
et al.1 and Pellicane et al.6; however, neither have been studied or validated.

Because most evidence for the treatment of CPSP is based on studies with a small number of subjects, large
clinical trials are needed to further assess existing and novel approaches to the treatment of CPSP.

REFERENCES

1. Klit H, Finerup NB, Jensen TS. Central post-stroke pain: clinical characteristics, pathophysiology, and
management. Lancet Neurol. 2009;8:857-868.
2. Andersen G, Vestergaard K, Ingeman-Nielsen M, Jensen TS. Incidence of central post-stroke
pain. Pain. 1995;61(2):187 – 193.
3. Harvey RL. Central poststroke pain syndrome. Top Stroke Rehabil. 2010;17(3):163-172.
4. Leijon G, Boivie J, Johansson I. Central post-stroke pain – neurological symptoms and pain
characteristics. Pain. 1989;36:13-25.
5. Kumar B, Kalita J, Kumar G, Misra UK. Central poststoke pain: a review of pathophysiology and
treatment. Anesth Analg. 2009;108(5):1645-1657.
6. Pellicane AJ, Harvey RL (2015). Central Poststroke Pain. In Stroke Recovery and Rehabilitation, Second
Edition (pp. 249-266). New York. NY: Demos Medical Publishing, LLC.
7. Bae SH, Kim GD, Kim KY. Analgesic effect of transcranial direct current stimulation on central post-stroke
pain. Tohoku J Exp Med. 2014; 234(3): 189-95.
8. Braus DF, Krauss JK, Strobel J. The shoulder-hand syndrome after stroke: a prospective clinical trial. Ann
Neurol. 1994;36(5):728-733.
9. Pellicane AJ, Millis SR. Efficacy of methylprednisolone versus other pharmacologic interventions for the
treatment of central-post stroke pain: a retrospective analysis. J Pain Res. 2013; 6: 557-563.
10. Baron R, Binder A, Wasner G. Neuropathic pain: diagnosis, pathophysiological mechanisms, and
treatment. Lancet Neurol. 2010;9:807-819.

Original Version of Topic

Anthony Pellicane, MD. Central Poststroke Pain. 11/10/2011.

Author Disclosure

Anthony Pellicane, MD
Nothing to Disclose

Source: https://now.aapmr.org/central-poststroke-pain-2/