Reference Work Entry

Encyclopedia of Neuroscience

pp 647-650

Central Pain

  • Troels S. JensenAffiliated withDepartment of Neurology and Danish Pain Research Center, Aarhus University Hospital
  • , Nanna B. FinnerupAffiliated withDepartment of Neurology and Danish Pain Research Center, Aarhus University Hospital


Thalamic pain; Deafferentation pain; Central neuropathic pain


The International Association for the Study of Pain (IASP) defines neuropathic pain as “Pain initiated or caused by a primary lesion or dysfunction of the peripheral or central nervous system.” A new classification is being introduced by a working group on Neuropathic pain. According to this working group, it is suggested that neuropathic pains are pains arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurological disorders and also distinguishes neuropathic pain from normal physiological plasticity seen when the somatosensory system is activated following noxious stimulation.

Central Pain (CP) occurs following lesions of the sensory pathways in the spinal cord or brain. The essential pathological feature is a lesion in the CNS resulting in partial or complete loss of sensory input in the nervous system with corresponding negative sensory phenomena, such as partial or complete anesthesia in the area subserved by the structure with the lesion [1]. In parallel with loss of input, ectopic activity, regeneration and disinhibition may take place resulting, in some cases, and with variable risk among different etiologies, in secondary development of hypersensitivity. A key issue in diagnosing CP is a detailed pain history and thorough neurological examination that should include a careful sensory examination, evaluating decreased or increased responses to touch, vibration, pinprick, and thermal stimuli as well as a mapping of the distribution of the sensory dysfunction (see also Neuropathic Pain).



A variety of diseases may give rise to CP (Table 1). The most common and well described central pains are central post-stroke pain and CP in spinal cord injury and multiple sclerosis, but any lesion along the sensory neuraxis from the dorsal horn to the brainstem, thalamus, subcortical white matter and probably cortical areas may cause CP [1]. Patients with Parkinson’s Disease, which is dominated by rigidity, bradykinesia and tremor, may also experience pain and sensory disturbances, but some of these pains may be related to dystonia and fluctuations in anti-parkinsonian medication [1]. Patients with epilepsy may have pain as part of a seizure or aura [1].
Central Pain. Table 1

Etiology of central neuropathic pain

Infarction or hemorrhage of brain or spinal cord


Multiple sclerosis


Syringomyelia or syringobulbia


Neoplasm of brain or spinal tissue


Spinal cord injury


Parkinson’s disease




Inflammation of brain or spinal cord tissue


Symptoms and Signs in CP

Central pains are characterized by a specific lesion or disease of the CNS and
  • Pain located in a neuroanatomical area with partial or complete sensory loss.

  • Spontaneous ongoing or paroxysmal pain (stimulus independent).

  • Stimulus evoked pain (stimulus dependent), including for example touch-evoked or cold allodynia, Hyperalgesia, abnormal summation of pain and after-sensations.

These symptoms/signs may occur in various combinations, but do not necessarily have to be present altogether. The underlying disease itself may also influence the pain and sensory pattern and contribute to heterogeneity of the core phenomena of CP.

Stimulus-independent pains are spontaneous pains and can be either continuous or paroxysmal. The character differs, but shooting, shock-like, aching, cramping, crushing, burning types of pain are descriptors that have been used. The pain may be described as superficial or deep or both. Other sensations such as paraesthesia and dysaesthesia may be present spontaneously or evoked (e.g., ongoing tight or tingling sensations evoked by touching the area). The onset of CP varies, but in most cases patients develop CP within three to six months after their central nervous system lesion. Any delayed onset of neuropathic pain should prompt an examination for other causes (e.g., syringomyelia in cases of spinal cord injury). After a stroke, CP may be distributed in a hemi body fashion or it may affect a smaller part of one side with sensory disturbance (e.g., part of a limb). In lateral medullary infarction, the symptoms may be crossed with pain in one side of the face and the other side of the rest of the body (Fig. 1).
Central Pain. Figure 1

Examples of distribution of central pain in a patient with central post-stroke pain following a lateral medullary infarction (a), a patient with at- and below level neuropathic pain in spinal cord injury (b), and a patient with central pain following multiple sclerosis (c).

In spinal cord injury, pain may be located at the level of injury as a band around the thorax, or below the level of injury, either diffusely or in patches (Fig. 1), while in syringomyelia, pain is often distributed in a segmental pattern. In multiple sclerosis, both hemi body pain and bilateral pain may occur (Fig. 1). Many patients report that the pain is increased by changes in weather, cold, psychological factors like stress or changes in mood.

Stimulus-dependent pains are classified according to the stimulus modality that provokes them (i.e., mechanical, thermal or chemical). Evoked pain is a common feature of CP patients [17]. Evoked pain is often present within the area of spontaneous pain, but may extend beyond this area or be present in patients without spontaneous pain. In spinal cord injury, patients may experience evoked pain below the level of injury in cases of incomplete spinal cord injury or in the border zone at the level of injury. There seems to be a correlation between evoked pain felt at the level of injury and spontaneous pain below the level of injury [4].

The most common and important forms of stimulus-dependent pains include allodynia, which implies that stimuli which normally do not provoke pain now do so. Allodynia may coexist with hyperalgesia. Non-noxious brush, touch or thermal stimuli are examples of stimuli that can give rise to allodynia. Allodynia may be present with little impact on the patient’s daily life; in other cases, it is the dominating clinical feature and very disabling. The touch from cloth or taking a shower may cause intense pain, and a gentle touch may be felt as a burning sensation. While allodynia usually is considered to be a cutaneous phenomenon, recent observations suggest the presence of a deep tissue allodynia. For example, in post-stroke pain, movement-induced pain has been described and deep pain may be associated with a lowering of pain threshold to mechanical pressure. Allodynia to touch is best assessed using cotton wool or a small brush and is assessed by brushing the skin lightly. This may elicit a burning pain sensation in patients with dynamic mechanical allodynia but also non-painful dysaesthesia. Allodynia to cold and warm stimuli may be assessed using thermo-rollers. In cases of pinprick hyperalgesia, the patient will report increased pain compared to the mirror site when pricked on the skin with a pin. After-sensations with continued pain long after the stimulation has ceased may be observed [see also Neuropathic Pain].

Sensory Deficits and CP

An essential part of neuropathic pain is loss of sensory function. In some cases, sensory changes are subtle and a thorough sensory examination is needed, including perhaps the use of quantitative methods. Abnormal temperature and pain sensibility is the most consistent abnormality in post-stroke pain and it is suggested that a spino-thalamo-cortical sensory deficit is a necessary, albeit not a sufficient condition for the occurrence of CP [24]. The sensory deficit may be dissociated from a decrease in thermal and pinprick sensations and a relative preservation of vibration and other somatosensory functions. In addition to the sensory deficits, some patients may have a paradoxical sensitivity to cold and heat such that cold is perceived as hot and vice versa.

Epidemiology of CP

There is limited information on the frequency of CP. In a prospective study that included 207 consecutive stroke patients, 8% developed CP within the first year after their stroke [2]. Lesions of the thalamus and lateral medullary infarction are associated with higher risks of developing CP. Multiple sclerosis pain is likewise frequent [6], and Österberg et al. reported that 28% of patients with multiple sclerosis have CP [7]. In spinal cord injury, CP occurs in about 30–45% [8]. Pain at the level of injury seems to have an early onset, while CP below the level of injury may develop later after the spinal injury. Both types of pain tend to persist despite attempts at management [8]. Although some studies have indicated a higher incidence of CP in patients with incomplete lesions, other studies suggest that there is no relationship between the extent or site of spinal lesion and the presence of pain. Older age at time of injury has been found to be related to spinal core injury neuropathic pain.

Mechanisms of CP

The mechanisms responsible for CP are still unclear, but various theories have been advanced to explain these pains. The frequent incidence of evoked pain and decreases in mechanical thresholds in painful areas suggest the presence of hyperexcitability, and clinical and experimental studies indicate the presence of sensitization of 2nd or 3rd order neurons in the CNS that have lost their normal patterned input [3]. After a central nervous system lesion, several changes, including release of glutamate, up-regulation of sodium channels, activation of glia and loss of inhibition, are thought to increase the excitability of central neurons from which abnormal input may arise. In addition, the thalamus is thought to play a key role in CP [3] and bursting activity and reorganization has been demonstrated in the thalamus following central lesions. Disinhibtion due to partial lesions and imbalance between pathways has also been suggested to contribute to the development of CP. Among the more interesting recent theories, Craig has suggested that CP is due to loss of a normal inhibitory effect exerted by cool-signaling pathways from lamina I projecting to the thalamus and insula [9]. According to this hypothesis, a lesion of the lateral cool projection system disinhibits the medial system of heat-pinch-cold neurons passing from Lamina I to the medial part of the thalamus. This disinhibition results in a release of cold allodynia, burning and ongoing pain [9]. Disruption of thermosensory integrations leads to a disinhibition of thalamocortical neurons that respond to noxious inputs and a sensation of burning pain [9].

Treatment of CP

Like other chronic pain conditions, CP is a complex psychological experience which may have consequences for daily activities, sleep, cognition, emotion, behavioral and social relations and a broad approach to the treatment is essential. There is limited data on the pharmacological treatment of CP. Gabapentin, pregabalin, tricyclic antidepressants, lamotrigine and cannabinoids are treatments that have been shown to relieve CP, but other drugs like serotonin-noradrenaline reuptake inhibitors and opioids have not yet been studied in CP conditions [10]. Gabapentinoids and antidepressants are often considered first drugs of choice, but as in other neuropathic pain conditions these drugs, even when given in effective and tolerable doses, only reduce pain to a variable extent and other drugs or drug combinations may be considered. Patients with CP often have concurrent medical problems and impairment, are treated with multiple drugs with unwanted side-effects, and they may be elderly, which should be considered when treating CP.

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