Guide to Pain Management in Low-Resource Settings

Management of Neuropathic Pain

179
Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th
  is material may be used for educational 
and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 
as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the 
medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th
  e mention of specifi c pharmaceutical products and any 
medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text.
Guide to Pain Management in Low-Resource Settings
Gaman Mohammed
Chapter 23
Painful Diabetic Neuropathy
Case report 1 (“neuroarthropathy”)
Zipporah, a 54-year-old woman, who has had type 2 di-
abetes for 12 years and is on oral hypoglycemic agents, 
came to the offi
  ce complaining about a history of leg 
pains, especially at night. She regularly walks to the lo-
cal market where she sells vegetables. She has noticed 
swelling on her legs over the last few months, but has no 
history of pain or trauma to the feet. Her husband Tom 
noted blisters on her feet a day after she had worn a new 
pair of sandals bought at her local market. Zipporah 
hadn’t felt any discomfort while wearing these sandals. 
Th
  e blisters had burst, revealing cuts over the feet, and 
her husband convinced her to seek medical attention af-
ter she unsuccessfully tried using home remedies such as 
bandaging the wound with an old cloth and cleaning the 
wound with salt solution.
Tests revealed an elevated random blood sugar 
of 15 mmol with an HbA of 11%. On visual examination 
she had bilateral foot edema with a septic lesion over 
both feet. Her foot pulses were present but feeble, prob-
ably as result of the edema. She had reduced vibration 
perception and pressure sensation in both feet. X-rays 
were suggestive of destruction of the talus and calcaneus 
bones in her feet.
On discussion with Zipporah, she was advised 
that in view of her current poor glycemic control and foot 
infections, insulin therapy had to be recommended to 
control the blood sugar. She was started on twice-daily 
insulin that she could also obtain at her local hospital 
and was given an antibiotic with a good Gram-positive 
and -negative eff ect. She was advised to have her daily 
dressing done at her local clinic and not use hydrogen 
peroxide solution on her injury. She was started on sim-
ple analgesics (paracetamol/acetaminophen) in combi-
nation with a weak opioid, tramadol. During follow-up 
review, she was started on amitriptyline at a low dose 
of 25 mg after she complained of burning sensations, es-
pecially at night. She was also given crutches and was 
advised to mobilize, with partial weight bearing, for a 
month as she mentioned she had to attend to her duties 
at the market.
Case  report  2  (60-year-old                                      
diabetic male on oral                   
hypoglycemic medication)
Yusuf, a 60-year-old man from a coastal city, has had 
diabetes for 6 years. He gave a history of severe burn-
ing sensations in his feet at night, which was relieved by 
placing his feet in a bucket of water. He didn’t seek medi-
cal treatment for his ailment until he noted a painful 
swelling of his toes of the right leg, although he did not 
remember having had an injury to the foot. Examination 
revealed that the right foot was infected, and the infec-
tion had spread to the interdigital spaces. He also had 
decreased vibration and pressure sensation, as tested by 
using a 10-g monofi lament and a tuning fork.

180
Gaman Mohammed
He was started on insulin, antibiotics, analgesics, 
and a tricyclic antidepressant and was given a thorough 
education on the importance of good glucose control and 
appropriate footwear. Local care was given. Yusuf re-
ported decreased pain at night and improved wound-site 
healing on his return visit to the offi
  ce approximately 3 
weeks later.
What is the scope of the problem?
Diabetes currently aff ects 246 million people world-
wide and is expected to aff ect 380 million by 2025. 
By 2025, the largest increases in diabetes prevalence 
will take place in developing countries. Unfortunate-
ly, these countries have economic burdens and con-
straints. More than 80% of the expenditure for medical 
care for diabetes is made in the world’s economically 
richest countries, and less than 20% in the middle- and 
low-income countries, where 80% of diabetics live. Th
 e 
WHO estimates that diabetes, heart disease, and stroke 
together will cost billions of dollars, even in a low-re-
source country like Tanzania.
Why is pain in patients                 
with diabetes an issue?
In diabetic patients, neuropathy is the most common 
complication and greatest source of morbidity and 
mortality, with an estimated global prevalence of ap-
proximately 20%, with the highest numbers being in 
African countries: Tanzania (25–32%), Zambia (31%), 
and South Africa (28–42%). Diabetic neuropathy is 
implicated in 50–75% of nontraumatic amputations in 
African countries.
Why do patients with diabetes 
develop neuropathy?
Th
  ere are four factors:
• Microvascular disease
•  Advanced glycosylated end-products
•  Protein kinase C
• Polyol pathway
What is microvascular disease?
Blood vessels depend on normal nerve function, and 
nerves depend on adequate blood fl ow. Th
 e fi rst patho-
logical change in the microvasculature is vasoconstric-
tion. As the disease progresses, neuronal dysfunction 
correlates closely with the development of vascular 
abnormalities, such as capillary basement membrane 
thickening and endothelial hyperplasia (thickening), 
which contribute to diminished oxygen supply and hy-
poxia. Neuronal ischemia is a well-established charac-
teristic of diabetic neuropathy. Vasodilator agents (e.g., 
angiotensin-converting-enzyme inhibitors) can lead to 
substantial improvements in neuronal blood fl ow, with 
corresponding improvements in nerve conduction ve-
locities. Th
 us, the microvascular dysfunction that oc-
curs early in diabetes parallels the progression of neu-
ral dysfunction and may be suffi
  cient to support the 
severity of structural, functional, and clinical changes 
observed in diabetic neuropathy. In addition, elevated 
intracellular levels of glucose lead to binding of glucose 
with proteins, thus altering their structure and destroy-
ing their function. Certain of these glycosylated proteins 
are implicated in the pathology of diabetic neuropathy 
and other long-term complications of diabetes.
Are analgesics the only treatment 
option in diabetic polyneuropathy?
Just the opposite! Glycemic control has a favorable ef-
fect on each of the microvascular complications of 
diabetes mellitus, both in preventing the onset of new 
complications and in slowing the progression of estab-
lished complications. Glycemic control should be an 
important cornerstone in pain control because pain as-
sociated with diabetic neuropathy decreases with im-
proved glycemic control.
Why does it hurt even though the 
patient does not “feel” anything, as 
is typical in diabetic neuropathy ?
Neuropathy in diabetics can present as sensory loss (in-
sensate) neuropathy or painful neuropathy. Th
 e major-
ity of people have the insensate type. However, approxi-
mately 4–7% of patients with diabetes suff er  chronic, 
often distressing symptoms of pain (“pins and needles”) 
or numbness in their feet. Why patients with diabe-
tes may develop painful neuropathy is not fully under-
stood, although it is known that patients with poorly 
controlled diabetes for a long time are more likely to 
get chronic painful neuropathy. Painful symptoms can 
be transient, often lasting less than 12 months. Th
 ese 

Painful Diabetic Neuropathy
181
symptoms are often associated with periods of high 
blood glucose levels, or paradoxically, may occur when 
blood glucose levels rapidly improve. In these acute sit-
uations, once the blood glucose has stabilized for a few 
months, the painful symptoms often spontaneously dis-
appear. Once symptoms have persisted for more than 12 
months, they are less likely to disappear on their own.
How did the patients mentioned 
above describe their pain, and what 
would be typical?
Pain associated with painful diabetic neuropathy is of-
ten described as tingling pain, numbness, or severe 
pain with stimuli that normally do not cause pain (“al-
lodynia”). It may also
 
be described as stabbing, deep 
seated, burning, electrical, or stabbing, with paresthesia 
or hyperesthesia. Typically, the pain develops in the feet 
and lower legs, but may also involve the hands, and it 
is normally greater
 
at night. Diabetic neuropathy aff ects 
the daily activities of the patient: sleep, independence, 
ability to work, interpersonal relationships, as well as 
mood. Although patients with painful diabetic neuropa-
thy typically voice their symptoms, many
 
patients may 
not report their symptoms until the pain is severe. In 
Africa and other developing regions in the world, where 
people often walk barefoot or have poor-fi tting and in-
appropriate footwear, diabetics with neuropathy may 
often have infected foot lesions, which can be painful. 
Th
  ey may have a history of minor injuries or at times 
they may not be aware of any injuries, despite evidence 
of trauma to the feet on examination. Approximately 
40–60% of all nontraumatic amputations are done on 
patients with diabetes, and 85% of diabetes-related low-
er-extremity amputations are preceded by foot ulcers. 
Four out of fi ve ulcers in diabetics are precipitated by 
external trauma.
If in doubt after taking the history, 
what may I do to confi rm the 
diagnosis of diabetic polyneuropathy?
Screening for neuropathy should be done annually for 
most diabetics. Any diabetic patient with a painless ul-
cer can be confi rmed to have diabetic polyneuropathy. 
Simple tests, using 128-Hz tuning fork, cotton wool, 
10-g monofi laments, and a patellar hammer, can reveal 
decrease in pressure or vibratory sensation or altered 
superfi cial pain and temperature sensation. Sensory loss 
due to diabetic polyneuropathy can be assessed using 
the following techniques:
How is the physical examination 
performed?
• Th
  e sensory examination should be done in a qui-
et and relaxed setting. First apply the tuning fork 
on the patient’s wrists (or elbow, or clavicle) so 
the patient knows what to expect.
• Th
  e patient must not be able to see if and where 
the examiner applies the tuning fork. Th
 e tuning 
fork is applied on a bony part of the dorsal side of 
the distal phalanx of the fi rst toe.
• Th
  e tuning fork should be applied perpendicular-
ly with a constant pressure.
•  Repeat this application twice, but alternate with 
at least one “sham” application, in which the tun-
ing fork is not vibrating.
• Th
  e test is positive if the patient answered cor-
rectly for two out of three applications. It is nega-
tive (“at risk for ulceration”) with two out of three 
incorrect answers.
•  If the patient is unable to sense the vibrations at 
the big toe, the test is repeated more proximally 
(malleolus, tibial tuberosity).
•  Encourage the patient during testing.
How is touch pressure sensation 
tested with a monofi lament?
A standardized fi lament is pressed against part of the 
foot. When the fi lament bends, its tip is exerting a 
pressure of 10 grams (therefore this monofi lament  is 
often referred to as the 10-gram monofi lament). If the 
patient cannot feel the monofi lament at certain speci-
fi ed sites on the foot, he or she has lost enough sensa-
tion to be at risk of developing a neuropathic ulcer. Th
 e 
monofi lament has the advantage of being cheaper than 
Pressure perception
Th
  e risk of future ulceration can be deter-
mined with a 10-gram monofi lament
Vibration perception
128-Hz tuning fork placed at the hallux
Discrimination
Pinprick (at the dorsum of the foot without 
penetrating the skin)
Tactile sensation
Cotton wool (at the dorsum of the foot)
Refl exes
Achilles tendon refl exes 

182
Gaman Mohammed
a biothesiometer, but to get results that can be com-
pared to others, the monofi lament needs to be calibrat-
ed to make sure it is exerting a force of 10 grams.
Advanced testing can be done using a biothesi-
ometer. A probe is applied to a specifi ed part of the foot, 
usually on the big toe. Th
  e probe can be made to vibrate 
at increasing intensity by turning a dial. Th
  e person be-
ing tested indicates as soon as he or she can feel the vi-
bration, and the reading on the dial at that point is re-
corded. Th
  e biothesiometer can have a reading from 0 to 
50 volts. It is known that the risk of developing a neuro-
pathic ulcer is much higher if a person has a biothesiom-
eter reading greater than 30–40 volts, if the high reading 
cannot be explained by age.
What are the pharmacological 
treatment options for painful 
diabetic neuropathy?
See Chapter 20 on Management of Postherpetic Neu-
ralgia for pharmacological analgesic treatment options, 
since the same principles for treatment of neuropathic 
pain apply.
What are complimentary 
approaches in management of 
painful diabetic neuropathy?
Sometimes the simple things maybe very eff ective; pa-
tients sometimes fi nd out what works for they and may 
be very inventive. Techniques often reported by patients 
to be very eff ective are:
•  Immersing the feet in a bucket of cold water
•  Placing the feet on a cold cement fl oor
•  Wrapping the feet with a cloth soaked in cold water
•  Gentle foot massage
•  Electromagnetic nerve stimulation or other local 
counterirritation (e.g., capsaicin cream)
Pearls of wisdom
•  Managing painful diabetic neuropathy continues 
to be a challenge in developing countries where 
resources are scarce and access to health care fa-
cilities is limited.
•  Diabetic patients often have poor follow-up or 
are seeking treatment at a late stage, when com-
plications associated with neuropathy have al-
ready set in.
•  On the other hand, primary care physicians may 
lack adequate knowledge and skills to screen for 
and treat diabetic neuropathy.
•  However, with basic knowledge on diabetic neu-
ropathy and appropriate management of diabetes, 
and with the help of simple screening tools such 
as tuning forks and monofi laments, early diagno-
sis and improved management of diabetic neu-
ropathy are possible.
•  Since a diverse range of mechanism cause pain in 
diabetic neuropathy, treatment principles should 
include a multifaceted approach aiming at im-
proving glucose control, targeting the underlying 
pathological factors, and treating the symptoms.
•  Painkillers are selected according to the princi-
ples of treating neuropathic pain.
•  Since pain often has a continuous burning quality, 
gabapentin or amitriptyline—possibly combined 
with a weak opioid—are typical choices for phar-
macological management of pain.
• Th
 e eff ectiveness of nonpharmacological treat-
ment options should not be underestimated.
References
[1]  Sorensen L, Wu M, Constantin D, Yue K. Diabetic foot disease: an in-
teractive guide. International Consensus on the Diabetic Foot.
[2]  Zachary T, Bloomgarden MD. Clinical diabetic neuropathy. Diabetes 
Care 2005;28:2968–74.

183
Guide to Pain Management in Low-Resource Settings, edited by Andreas Kopf and Nilesh B. Patel. IASP, Seattle, © 2010. All rights reserved. Th
  is material may be used for educational 
and training purposes with proper citation of the source. Not for sale or commercial use. No responsibility is assumed by IASP for any injury and/or damage to persons or property 
as a matter of product liability, negligence, or from any use of any methods, products, instruction, or ideas contained in the material herein. Because of the rapid advances in the 
medical sciences, the publisher recommends that there should be independent verifi cation of diagnoses and drug dosages. Th
  e mention of specifi c pharmaceutical products and any 
medical procedure does not imply endorsement or recommendation by the editors, authors, or IASP in favor of other medical products or procedures that are not covered in the text.
Guide to Pain Management in Low-Resource Settings
Chapter 24
Management of Postherpetic Neuralgia
Maged El-Ansary
Case report
As a general practitioner, you receive a 75-year-old male 
patient with a history of diabetes mellitus. He has had 
bronchogenic carcinoma and is currently on chemo-
therapy. He has pain in the left side of the chest along the 
distribution of the 5th, 6th, and 7th intercostal nerves. 
What is your possible diagnosis?
Th
  e possibilities are myositis, coronary ischemia, 
left-sided pleurisy, fractured ribs, itching due to skin al-
lergy or drug eruption or other causes, such as the pre-
eruptive stage of acute herpes zoster.
Why is postherpetic neuralgia 
diffi
  cult to treat?
Postherpetic neuralgia (PHN) is known to be one of the 
most resistant chronic pain problems. It is classifi ed as a 
neuropathic pain state. Th
 e signifi cance is that the pain 
is coming from nerve lesions due to viral infections at 
the site of spinal nerve roots.
Not only pain fi bers of the nerve but also sym-
pathetic and tactile fi bers, and in rare occasions motor 
fi bers, may be involved in the syndrome. Remember: 
you can only make a diagnosis if you undress your pa-
tient and look at the site of pain.
When is pain after herpes zoster 
called postherpetic neuralgia?
Most experts agree that pain lasting longer than 3 
months after an acute herpes infection (“shingles”) should 
be called postherpetic neuralgia. Th
  is has a therapeutic 
consequence because spontaneous remission of pain be-
comes more unlikely after this period of time. Th
 erapeu-
tic eff orts should be increased if pain lasts longer than a 
couple of weeks.
Is acute pain a predictor of an 
outcome of postherpetic neuralgia?
Unfortunately, there are no accepted and validated fac-
tors for predicting the severity and duration of pain af-
ter herpes infections. Pain may be almost or completely 
absent in patients who develop PHN. But for the elderly, 
as pain can start before the skin changes, hemorrhagic 
effl
  orescence and a location outside the trunk might in-
dicate a high-risk patient.
Are pain management and antiviral 
therapy suffi
  cient to treat a patient 
with herpes zoster?
It is wise to summarize acute herpes zoster as a sign of 
an alarmingly low level of immunity. It should be known 
that acute herpes zoster and PHN could indicate a wide 
range of underlying diseases. In many regions of the 
world, the fi rst diseases to consider underlying shin-
gles are immune-compromised diseases such as HIV/
AIDS and/or malnutrition. Early use of antiviral drugs 
and pain treatment in the early stages of the acute her-
pes zoster will have an impact on the course of an acute 
attack and the possibility of lowering the incidence of 

184
Maged El-Ansary
PHN, but there are no evidence-based studies to prove 
this point.
Diagnosis
Which other conditions must be considered 
when herpes zoster is diagnosed?
When taking the medical history, the patient’s age, sex, 
and race and certain psychosocial factors will guide you 
to the proper diagnosis. Diff erent age groups would in-
dicate certain probable causes. One should be aware of 
other possible causes, which may be present depending 
on the age group.
•  Headaches (present as a general response to viremia)
•  Appearance of red skin areas (2–3 days later)
• Th
  e patient cannot tolerate his clothes due to hy-
persensitivity of the skin (which may be misdiag-
nosed as urticaria with histamine release)
•  Typical painful vesicles (blisters) will appear that 
are full of serous fl uid (3–5 days later)
•  Blisters full of pus will break down and start to 
crust over (2–3 weeks later)
• Th
  e crusts will heal and itching stops, but pain 
persists along the distribution of the nerve (after 
another 3–4 weeks)
In rare cases the above symptoms will be ac-
companied by muscle weakness or paralysis if the 
nerves involved also control muscle movement.
What are the most common nerves aff ected by 
herpes zoster?
Trigeminal nerve
Trigeminal neuralgia (all three branches, ophthalmic 
branch infection: a dendritic ulcer of the cornea may 
develop as a serious complication, possibly causing cor-
neal opacity).
Cranial nerve VII
With severe tinnitus, the patient complains about hear-
ing loud bells or humming in the head, which may drive 
some patients to suicide.