Definition

Central post-stroke pain (CPSP), formerly known as thalamic pain syndrome, is a chronic complex disabling pain syndrome characterized by pain and temperature sensation abnormalities after a cerebrovascular accident, infarct, or hemorrhage. It was first described, with pathophysiologic correlation to a lesion in the thalamus, in 1906 by Dejerine and Roussy as a “severe persistent, paroxysmal, often intolerant pain on the hemiplegic side, not yielding to analgesic treatment” [1]. There were previous descriptions of pain after a central lesion by Edinger [2] and others earlier in the 19th century.

The disease affects up to 8% of patients with stroke and, in one study, 9% of hemorrhagic stroke patients with thalamic lesions [3–5]. Pain onset in stroke patients occurs weeks to months after a cerebrovascular accident [5]. CPSP is considered a persistent central neuropathic pain that follows an ischemic or hemorrhagic stroke without a peripheral cause. Although the pathogenesis remains unclear, there appears to be involvement not only of the thalamus as initially studied by Dejerine but of the spinothalamic pathway because of the pain and temperature sensitivity [6,7]. Interestingly, not all patients with lesions along the spinothalamic pathway have CPSP [8,9]. Many CPSP patients have many lesions noted on magnetic resonance imaging that are unrelated to the pain [10].

Predictors as to those at risk are unclear, but in one study controls with thalamic stroke without thalamic pain had lesions mainly in the more anterolateral nuclei. Thalamic pain patients were noted to have lesions mainly in lateral and posterior thalamic nuclei on magnetic resonance imaging [11]. In one study at 16 months, patients with higher pain intensity were female [12].

Symptoms

CPSP is characterized by mild hemiplegia, hemihypoesthesia, hyperpathia with burning sensation, hemiataxia, astereognosis, dyskinesias (especially choreoathetosis), and positive or negative pain sensations that occur for hours to continuously in the entire half the body, arm, leg, foot, or hand [13,14]. Patients describe pain sensations as burning, cold, stabbing, sharp, aching, pricking, squeezing, shooting, tingling, or heavy when they are exposed to changes in temperature measured by a thermal probe, monofilament for tactile stimuli, and brushing with a stiff brush typically used for oil painting [15]. Particularly excruciating are the sensory abnormalities, especially the thermal sensations that can include burning, scalding, or burning and freezing in addition to other vague descriptions of positive and negative sensory abnormalities. Symptoms can be constant or intermittent, described as burning by some CPSP patients, and triggered by touching of an item, being touched, or changes in temperature [14]. Because of the variable onset and symptom constellation, patients are often misdiagnosed [16].

Physical Examination

It is important in considering the diagnosis of CPSP to perform a thorough musculoskeletal and neurologic physical examination to rule out other causes of pain. Physical findings in patients with CPSP may include mild or more severe hemiplegia, hyperesthesia, or hypoesthesia. Patients may have impaired pinprick, temperature, and touch sensation, whereas vibration and joint proprioception are less commonly affected [10].

In a prospective study of 207 stroke patients, 87 subjects (16 with CPSP and 71 with no pain) with abnormal sensation were observed. The CPSP group was noted to have more abnormal sensibility to cold and warm stimuli compared with nonpain subjects with abnormal sensation. The 16 CPSP patients had evoked dysesthesia or allodynia (sensation of pain by stimuli that are usually nonpainful) [5].

Functional Limitations

Strokes that cause CPSP are typically associated with only mild hemiplegia, though some patients can have moderate or severe hemiplegia and the functional limitations that accompany these. The pain of CPSP can often be a much more severe cause of functional limitation, at times to the point of being incapacitating.

Diagnostic Studies

Brain imaging of patients with CPSP will typically show a lesion in the spinothalamic pathway, but not all patients with such lesions will have CPSP [8,9].

Historically, CPSP has been resistant to both medical and surgical management. Despite the severe impact on quality of life for patients with CPSP, there is limited scientific evidence of its treatment [17].

The only medications that have shown pain reduction in a randomized controlled trial are amitriptyline (at least 75 mg daily) [18], lamotrigine (at least 200 mg daily) [19], and gabapentin [20]. Thus, these medicines are considered first-line management for CPSP. Unfortunately, even with these medicines, only mild pain relief was achieved, and many patients did not respond at all. Other medicines that have been found to have some benefit in open trials, such as nortriptyline, desipramine, imipramine, doxepin, venlafaxine, maprotiline, gabapentin, pregabalin, carbamazepine, mexiletine, fluvoxamine, and phenytoin, are considered second-line treatment [10,17–19,21–28].

For patients resistant to treatment, opioids (such as levorphanol, studied in a double-blind randomized controlled study) have been used, resulting in some pain reduction in a small group but not in a large population [29]. In one study, intravenous morphine showed a modest short-term benefit in some patients [30]. Long-term benzodiazepines are not recommended because of potentiation of inhibitory effects of γ-aminobutyric acid, but there is a possible role of short-term use in CPSP patients with anxiety [13]. Intravenous administration of the γ-aminobutyric acid agonist thiopental, intravenous propofol, and intrathecal baclofen alleviated some pain in patients with CPSP [31–33], but oral doses of baclofen and amobarbital were ineffective [33,34].

Rehabilitation

Rehabilitation begins with management of the various deficits resulting from the stroke. Barriers to treatment include cogitative and communication limitations due to the cerebrovascular event [16].

To date, CPSP has been difficult to treat with medical or surgical interventions [16]. The pain in CPSP is a “false” signal being generated by the brain. Pain can be a useful symptom indicating an injury, but in CPSP there is no corporeal injury. It would be ideal if some method could be found to “connect to” and retrain the thalamus or other brain areas to the fact that there is no injury, so there should be no pain. For movement problems after stroke, mirror therapy [35], in which visual feedback from the reflection of the good limb helps regularize the motor control loop, can be beneficial [36]. This approach does not work for CPSP (even in patients with CPSP and hemiparesis after stroke for whom mirror therapy helped the hemiparesis), nor should one expect it to because the problem is sensory pain, not a movement difficulty.

Procedures

There has been one case report finding acupuncture helpful in CPSP [37]. Acupuncture, perhaps by sensory stimulation, may be a way to “reconnect” with and retrain the thalamus or associated structures. Further studies of acupuncture for CPSP are warranted.

Surgery

When all other modalities have failed, deep brain stimulation has been tried in a couple of cases. For example, one male patient had some improvement in pain at 6-month follow-up [38]; another male patient with deep brain stimulation by an electrode implanted in his periventricular gray region had pain relief lasting 4 months [39].

Neurosurgical destructive options include medial thalamotomy and mesencephalic tractotomy, which in limited cases of patients with central and deafferentation pain improved the allodynia and hyperpathia, but with less promising outcome for the burning or dysesthetic pain [40]. As ablation is considered the final resort, more conservative measures, including deep brain stimulation, should be tried.

Potential Disease Complications

Disease complications include severe pain and its typical sequelae that affect the quality of life of the individual with CPSP. Because of the physical and psychological effects of central pain, work and social life are often affected, requiring different cognitive and behavioral techniques to cope [41]. In one study, 27 patients with CPSP reported pain to be a great burden, and most rated the intensity as high, interfering more with leisure activities compared with brainstem lesions [42]. Problem-centered coping with focus on external or environmental etiology is used more often by men, whereas emotion-centered coping is more often used by women. For example, women in one group were noted to use spiritual and religious activities as coping strategies more often than men did [41].

Potential Treatment Complications

Treatment complications include adverse effects of the medications or surgical procedure and vary by the medication or surgery implemented. It is important to consider and to minimize drug interactions in patients, especially those who are taking multiple medications as these patients often are.