Guide to Pain Management in Low-Resource Settings

Guide to Pain Management in Low-Resource Settings
Chapter 25
Central Neuropathic Pain
Maija Haanpää and Aki Hietaharju
Case report 1
Abdul Shamsuddin, a 35-year-old shopkeeper from 
Gulshan, Dhaka, was found by his wife lying on the fl oor 
of his apartment. He was brought into the hospital on a 
makeshift stretcher carried by four relatives, all saying 
diff erent things about what had happened. In the emer-
gency room, he was conscious but not able to move his 
legs or left arm. He was complaining of severe burning 
pain in his right hand and deep aching pain in both of 
his upper extremities. Th
  e man explained, incoherently, 
that his house had been entered by a gang of robbers, 
and the last thing he remembered was a loud gunshot. A 
lacerated wound 1 cm in diameter was revealed on ex-
amination of his neck. Neurological examination showed 
total loss of sensation below T2. Th
  ere was severe hyper-
esthesia, hyperalgesia, and dynamic allodynia as well as 
impaired cold sensation in the 4th and 5th fi ngers  and 
on the ulnar side of his right hand. In the left hand, there 
was mild dynamic allodynia, and hyperalgesia was no-
ticed in the 3rd fi nger.  Th
  e patient was able to fl ex  his 
right arm and lift his hand up against gravity. A radio-
graph of the cervical spine showed a posterior arch frac-
ture of C7 and a 9-mm bullet lying close to the scapula 
on the right side. MRI of the cervical spine showed spinal 
cord contusion extending from the C4 to T2 level. Th
 e 
continuity of the spinal cord was intact, and no signs of 
hematoma were present.
Th
 is case shows that neurological injury and 
spinal cord pain can occur even if a projectile does not 
penetrate the spinal canal. Cord contusion was prob-
ably the result of the kinetic energy transmitted by the 
bullet. Th
  e patient’s pain medication included amitrip-
tyline and gabapentin. Within 4 years, the neuropathic 
pain started gradually to resolve, and gabapentin was 
successfully tapered off .
Case report 2
Shabana, an Afghan housewife from Jalalabad in her 
late thirties, came to a psychiatric outpatient clinic es-
corted by her husband. She had suff ered for more than 
2 years from continuous burning pain in her left hand 
and the right side of her face. She had been referred to 
the psychiatrist by a general practitioner who, due to 
Shabana’s infertility, had assumed a psychogenic basis 
as the cause of her pain. History taking revealed that she 
had had a sudden attack of vertigo, slurred speech, and 
motor weakness in her left extremities 3 years earlier. 
She had not consulted her doctor at that time. Most of 
her symptoms had subsided within 2 days, but the mo-
tor weakness had persisted for weeks. She reported that 
the painful symptoms had appeared about 2 months 
after this attack. Neurological examination revealed 
slight clumsiness and ataxia in her left arm, but muscle 
strength was regarded as normal. A conspicuous de-
crease in cold and pain sensibility was noticed on her 
right cheek, and in the lower two-thirds of her left arm as 
compared to the contralateral side. Cardiac auscultation 
did not reveal a pathological rhythm or sounds. Due to 

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Maija Haanpää and Aki Hietaharju
lack of resources, brain imaging was not available. Based 
on the history and clinical fi ndings, a tentative diagno-
sis of central neuropathic pain due to a low brainstem 
infarct was made. She was started on amitriptyline and 
prophylactic acetylsalicylic acid (100 mg/day).
What does “central           
neuropathic pain” mean?  
By defi nition, neuropathic pain arises as a direct con-
sequence of a lesion or a disease aff ecting the somato-
sensory system. In central neuropathic pain, the lesion 
can be located anywhere in the spinal cord or the brain, 
aff ecting the spinothalamocortical pathways (Fig. 1). 
Th
  erefore, the older concept of “thalamic pain” is in-
correct: the lesion may be at any level of the central 
nervous system (CNS). Musculoskeletal and visceral 
nociceptive pains are also common in patients with 
CNS diseases caused by conditions such as spasticity 
or bladder dysfunction, but these pains are not includ-
ed in the concept of central neuropathic pain. Acute 
headaches caused by a stroke or head trauma are not 
regarded as neuropathic pain, either. Th
  ey are classifi ed 
as secondary headaches and are due to distension or ir-
ritation of meninges.
What diseases can cause central 
neuropathic pain?
Possible causes of central neuropathic pain are listed in 
Table 1.
How common is central 
neuropathic pain?
Th
  e most common brain disease causing central pain is 
stroke. About 8% of patients who have had a stroke de-
velop central poststroke pain. With an annual incidence 
of 117–219 per 100,000 in the European population, 
and 83–329 per 100,000 in the Japanese and Chinese 
population, stroke represents one of the greatest public 
health problems worldwide.
Th
  e most common cause of spinal cord pain is 
trauma. About 70% of patients with spinal cord injury 
are aff ected with central neuropathic pain. It has been 
estimated that the annual incidence of spinal cord injury 
in diff erent countries throughout the world varies from 
15 to 40 cases per million.
Th
 e prevalence of neuropathic pain is not 
known in rarer conditions, such as syringomyelia or spi-
nal tuberculosis. Although central neuropathic pain is 
relatively uncommon, its impact should not be under-
estimated, because it is diffi
  cult to treat and causes dis-
ability and suff ering to those aff ected.
What are the clinical characteristics 
of central neuropathic pain?
A common feature of central neuropathic pain is al-
tered function of the spinothalamic tract, which medi-
ates temperature and pain sensations. Hence, abnormal 
temperature or pain perception or both is found in sen-
sory testing. Patients usually experience constant spon-
taneous pain, but they can also have pain paroxysms 
(brief attacks of pain), evoked pain (pain caused by a 
stimulus), and allodynia (innocuous stimuli are sensed 
as painful). Pain may be sensed as deep, superfi cial, or 
both. It may be exacerbated by changes in mood, envi-
ronmental temperature, and physical conditions, and 
relieved if attention is directed to some interesting issue. 
Central neuropathic pain is often described as intense, 
annoying, and exhausting, although it may be mild in 
some patients. Th
  e most common qualities of central 
pain are burning, pricking, and pressing.
CNS lesions may also cause other neurological 
symptoms and signs, such as motor paresis, ataxia, ab-
normal vision, or disturbed bladder function, depend-
ing on the location and size. Th
 ere is no association 
between pain intensity and the presence or absence of 
accompanying symptoms, which can be even more dis-
abling than the pain in some patients.
Table 1
Causes of central neuropathic pain
Spinal Cord
Brain
Trauma
Trauma
Multiple sclerosis
Multiple sclerosis
Vascular lesion (infarction, 
hemorrhage, arteriovenous 
malformation)
Vascular lesion (infarction, 
hemorrhage, arteriovenous 
malformation)
Infectious diseases (spinal tuber-
culosis, HIV, syphilitic myelitis, 
epidural abscesses with spinal 
cord compression)
Infectious diseases (tuberculo-
mas, cerebral abscesses)
Tumors
Tumors
Subacute combined degenera-
tion of the spinal cord due to 
vitamin B
12
 defi ciency
Dysraphism
Syringomyelia

Central Neuropathic Pain
191
For the diagnosis of central neuropathic pain, 
the neuroanatomical location of the lesion should be 
determined (Fig. 1). A lesion in a brain hemisphere 
causes abnormal fi ndings on the contralateral side of the 
body. A lesion in the brainstem causes abnormal cranial 
nerve fi ndings on the ipsilateral side, whereas abnormal 
fi ndings in the limbs and trunk are due to a contralateral 
lesion. A lesion in the spinal cord causes abnormal fi nd-
ings below the lesion level.
Central neuropathic pain may be present from 
the start of the neurological symptoms or appear with 
a delay of days, months, or even years. In the delayed 
cases, a repeat neurological examination is mandatory 
to identify whether it is a new event or a progression of 
the previous disease (e.g., a new stroke, or syringomy-
elia with expanding sensory loss after the spinal cord in-
jury). After it appears, central neuropathic pain tends to 
become chronic, typically continuing for many patients 
for the rest of their lives.
What is meant by traumatic     
spinal cord injury?
Various traumas may result in dislocation and fracture 
of spinal vertebrae and cause spinal cord injury. In ad-
vanced countries, road traffi
  c accidents rank highest 
among the etiological factors for traumatic spinal cord 
injury. According to an epidemiological study conduct-
ed in Haryana, India, the predominant cause of injury 
was falling from a height (45%), followed by motor vehi-
cle accidents (35%). Other causes of spinal cord trauma 
include sports injuries and acts of violence, primarily 
gunshot wounds. In people with asymptomatic cervical 
spinal stenosis, a fall or a sudden deceleration force can 
cause a contusion in the cervical cord, even without any 
bone or joint trauma. Spinal cord injury can be partial, 
saving some motor or sensory functions or both, or it 
can be complete, causing paralysis and complete senso-
ry loss below the level of the lesion.
What are the characteristics 
of central neuropathic pain in      
spinal cord injury?
Pain following spinal cord injury is divided into below-
level pain and at-level pain. Th
  e latter is located in a 
segmental or dermatomal pattern, within two segments 
above or below the level of spinal cord injury. It may be 
due to damage of the spinal cord itself or nerve roots. 
In cases of nerve root damage, the pain may have uni-
lateral predominance. Below-level pain is typically con-
stant, severe, and diffi
  cult to treat and represents central 
deaff erentation-type neuropathic pain. If the lesion is 
partial, the sensory fi ndings may be patchy, whereas in a 
complete lesion there is total loss of sensation below the 
level of the injury.
Is all pain neuropathic in patients 
with spinal cord injury?
Patients with spinal cord injury and central neuropathic 
pain may often have concomitant nociceptive muscu-
loskeletal pain due to muscle spasms or overuse of the 
normally functioning parts of the body (e.g., the upper 
limbs and shoulders in paraparesis). Examples of com-
mon visceral nociceptive pains in these patients are pain 
caused by bowel impaction or distension of the bladder. 
Th
  ese symptoms are important to recognize in manage-
ment of the patient with spinal cord injury.
What is syringomyelia?
Syringomyelia is a cystic cavitation of the central spinal 
cord, most commonly in the cervical region. It can be 
developmental, as in Chiari I malformation, or acquired, 
usually due to traumatic spinal cord injury. It is clinically 
characterized by segmental sensory loss, which is typi-
cally of a dissociated type, in which thermal and pain 
sensations are lost but tactile and proprioceptive sensa-
tions are preserved. Pain in cervical syringomyelia can 
be located in the hand, shoulder, neck, and thorax, is 
often predominantly unilateral (ipsilateral to the syrinx), 
and can be exacerbated by coughing or straining. Auto-
nomic symptoms such as changes in skin temperature 
or sweating in the painful area can also be present. Pain 
may be the fi rst symptom, or it may appear after a long 
delay after the original lesion. Motor weakness may ap-
pear with the progression of the disease. Neurosurgical 
treatment is considered only in cases with recent and 
quick progression.
What is phantom limb pain?
After traumatic amputation, at least half of patients 
experience phantom limb pain, which refers to pain 
experienced in the lost part of the body. It is related 

192
Maija Haanpää and Aki Hietaharju
to central reorganization in the cerebrum, which ex-
plains the peculiar phenomenon of pain experienced 
in the missing part of the body. In some patients, phan-
tom limb pain is maintained by stump pain (a periph-
eral pain at the site of amputation). Phantom limb pain 
is more likely to occur if the individual has a history of 
chronic pain before the amputation and is less likely if 
the amputation is done in childhood.
Phantom pain is often similar to the pain felt 
before the amputation, and in addition, the patient may 
experience nonpainful phantom phenomena, such as a 
twisted leg.
Graded motor imagery and mirror therapy 
are novel and inexpensive approaches that have been 
shown to reduce pain and disability in patients with 
phantom limb pain. In graded motor imagery, patients 
go through three phases. First, they assess images 
of their limbs in various positions. Th
  e second phase 
consists of imagining moving the limbs in a smooth 
and painless manner. Finally, patients end up by actu-
ally mimicking the movement. In mirror therapy, pa-
tients are instructed to use the mirror in such a way 
that the refl ected image of the intact limb seems to 
appear in the place of the amputated or aff ected  ex-
tremity. Th
  e mirror image produces an illusion of two 
“healthy” limbs, and movement of the healthy limb 
may ameliorate the phantom limb pain. Both of these 
therapies aim at activation of cortical networks that 
subserve the aff ected limb. 
What is the defi nition of central 
poststroke pain?
All neuropathic pain directly caused by cerebrovascu-
lar lesion (i.e. infarct or hemorrhage), independent of 
where the lesion is located, is called central poststroke 
pain. It was previously called thalamic pain according to 
the typical location of the lesion, but it can also be due 
to cortical (parietal cortex), subcortical, internal capsule 
(posterior limb), or brainstem lesion.
What are the clinical features of 
central poststroke pain?
In the majority of patients, central poststroke pain is 
a contralateral hemi-pain, not always including the 
face, but it may also be restricted to part of the upper 
or lower extremity. Th
  e most common pain quality is 
burning pain, but aching, pricking, and lacerating pain 
is also common. Central poststroke pain is most often 
constant and spontaneous, but in rare cases it may be 
paroxysmal and allodynic (i.e., evoked by touch, ther-
mal sensation, or emotions). Hyperesthesia is a com-
mon fi nding in sensory examination. In a hemisphere 
lesion, there is abnormal sensation on the contralateral 
side of the face, trunk, and limbs, and accompanying 
motor paresis if the pyramidal tract is aff ected. In a low 
brainstem lesion, there is a crossed pattern in the sen-
sory changes: they are located ipsilaterally in the face 
and contralaterally in the trunk and limbs due to dam-
age of the ipsilateral trigeminal sensory nucleus and the 
crossed spinothalamic tract, respectively.
Is all pain neuropathic in patients 
who have had a stroke?
Nociceptive pain is also very common in patients who 
have had a cerebrovascular lesion. It most often aff ects 
the shoulder and is related to changed dynamics due to 
motor weakness on the aff ected side. Possible causes are 
subluxation of the glenohumeral joint, rotator cuff  tear, 
soft tissue injury due to inappropriate handling of the 
patient, and spasticity of the shoulder muscles.
What are the characteristics 
of central pain after traumatic      
brain injury?
Traumatic brain injury occurs when a sudden, blunt, or 
penetrating trauma causes brain damage. Th
 e preva-
lence of central pain in patients with traumatic brain 
injury is not known. Chronic pain in these patients is 
almost exclusively unilateral, and the most common 
qualities are pricking, throbbing, and burning. A curi-
ous feature is the manifestation of pain in body regions 
that are not associated with local or spinal injury. Th
 ese 
painful regions exhibit very high rates of pathologically 
evoked pain (allodynia and hyperpathia). Th
  e most fre-
quently reported painful body regions are the knee area, 
shoulders, and feet. Neuronal hyperexcitability has been 
suggested as a contributing factor to the chronic pain. 
Treatment of central pain in patients with traumatic 
brain injury is challenging, because most of these pa-
tients are also suff ering from cognitive defi cits and emo-
tional distress, and neuropathic pain may overlap with 
pain of psychogenic origin.

Central Neuropathic Pain
193
How can I diagnose central 
neuropathic pain?
Th
 e cornerstones of the diagnosis are a detailed his-
tory of development of symptoms and relieving and ag-
gravating factors, and a careful neurological examina-
tion including sensory testing to touch, pinprick, cold, 
warmth, and vibration. Abnormal sensory fi ndings sug-
gest the possibility of neuropathic pain, and other neu-
rological fi ndings help to localize the site of the lesion. 
It is important to keep in mind that the region of sen-
sory abnormalities may be larger than the painful region 
(Case 2). Diagnosing central neuropathic pain is actu-
ally identifying symptoms and neurological signs com-
patible with a lesion in the CNS, and excluding other 
possible causes of pain. Typical neurological fi ndings 
referring to a central neurological lesion are a positive 
Babinski sign, accelerated tendon refl exes, and spastic-
ity. Other possible causes of pain need to be excluded 
with reasonable certainty. Careful clinical examination 
is usually suffi
  cient for this process, such as diagnosing 
musculoskeletal pain or pain due to local infection.
Diagnostic studies, such as neuroimaging and 
cerebrospinal fl uid analysis, may provide useful infor-
mation in reaching an accurate diagnosis, but they may 
not be available. In such conditions, recognition of the 
clinical features of the causative diseases is very useful. 
Th
  e decision as to the use of limited resources and se-
lection of patients for referral is based on the possibili-
ties of treatment of the causative disease, such as with 
neurosurgery. Spinal and cerebral abscesses, spinal trau-
mas with partial cord lesion, and spinal tumors are ex-
amples of conditions with radically improved prognosis 
with active surgical treatment. Cerebral abscess should 
be suspected if a patient has fever and progressive neu-
rological symptoms (in cerebral abscess contralateral 
symptoms, and in spinal abscess sensory and motor de-
terioration below the level of the abscess). 
History of trauma before the onset of weak-
ness of the limbs and sensory changes, including central 
pain, is suggestive of partial cord lesion. If there is an 
unstable lesion of the vertebral column, quick stabilizing 
surgery may prevent complete paralysis, and the same is 
true with laminectomies in spinal contusion with par-
tial paresis. Slowly progressive paraparesis and sensory 
changes may be caused by a spinal tumor. Removal of 
the tumor may prevent paralysis. Th
 e fi nal  prognosis 
depends on the histology of the tumour and the severity 
of the symptoms before surgery. Treatable intracranial 
hematomas usually present with headache and progres-
sive neurological symptoms, but central neuropathic 
pain is an uncommon symptom in these cases.
How should the patient be treated?
Treatment consists of:
•  Treatment of the causative disease, when possible 
(e.g., medical and surgical treatment of epidural 
abscesses causing spinal cord compression).
• Secondary prevention (e.g., commencing ace-
tylsalicylic acid prophylaxis for atherothrom-
botic cerebral infarct, or treating endocarditis in 
a patient with embolus from an infected cardiac 
valve).
•  Symptomatic relief of the neuropathic pain.
•  Treatment of other concomitant sources of pain 
such as spasticity, which may exacerbate central 
neuropathic pain.
Th
 e fi rst line of therapy, after a thorough assess-
ment, is information and education, for both the patient 
and the family. For example, phantom limb pain is dif-
fi cult to understand for a layman. Th
  e doctor’s explana-
tion in this situation may be very helpful (“your father 
is not crazy having pain where he has lost a limb”). Th
 e 
character of the pain, the disease causing it, and the 
possibilities for pain relief need to be explained to the 
patient and the family. As symptomatic treatment of 
central neuropathic pain is less successful than treat-
ment of peripheral neuropathic pain, giving thorough 
information may be the best way to help the patient.
Similarly to peripheral neuropathic pain, antide-
pressants and anticonvulsants are used for symptomatic 
treatment of central neuropathic pain. Amitriptyline 
is the drug of choice for central poststroke pain. It is 
started with 10–25 mg in the evening, and the dose is 
escalated by 10–25 mg steps to 50–150 mg/day depend-
ing on the extent of side eff ects. Diffi
  culties in urination, 
constipation, dry mouth, and dizziness are typical side 
eff ects, which may prevent further dose escalation. Ar-
rhythmias caused by amitriptyline contraindicate its 
further use. If amitriptyline is intolerable or ineff ective, 
carbamazepine can be tried instead. It is started at 100 
mg b.i.d., and the dose is escalated in 100-mg steps over 
several days until 400–800 mg/day is reached. If side ef-
fects (dizziness, headache, ataxia, or nystagmus) appear, 
the dose should be reduced.
Pregabalin has been shown eff ective for spinal 
cord injury pain, but it is not available in every country. 

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Maija Haanpää and Aki Hietaharju
Gabapentin has the same mechanism of action and can 
be used instead. It is started with 300 mg in the evening, 
and the dose is escalated in steps of 300 mg daily or ev-
ery other day. Th
  e daily dose is divided into three dos-
es. Th
 e eff ective dose is 900–3600 mg/day, divided into 
three daily doses. Gabapentin has no pharmacokinetic 
interactions. It can be tried also for central poststroke 
pain if amitriptyline and carbamazepine fail.
Central neuropathic pain is unfortunately quite 
refractory to treatment, and pain relief is usually only 
partial. Based on information from open studies and 
clinical experience, transcutaneous electrical nerve 
stimulation (TENS) can be helpful for central pain in 
cases where there is well-preserved sensibility to vibra-
tion and touch.