Guide to Pain Management in Low-Resource Settings

Pearls of wisdom
•  Know which common analgesics are considered 
safe in early pregnancy, and know where to fi nd 
an information resource describing drug safety 
in pregnancy and lactation. Be guided by pub-
lished recommendations and liaise with other 
medical and nursing staff  involved in pain man-
agement.
• Choose a postoperative analgesic regimen af-
ter cesarean section that is not only eff ective but 
also minimizes neonatal drug exposure through 
breast milk. Th
  ere should be a multimodal opi-
oid-based approach, preferably using the spinal 
(subarachnoid) route of opioid administration. If 
a systemic opioid is used it should be combined 
with nonopioid analgesics and/or a regional an-
algesic method (e.g., the transversus abdominis 
plane block).
•  Use of opioids during pregnancy does not cause 
fetal malformations but may result in neonatal re-
spiratory depression at birth and a neonatal absti-
nence syndrome starting the fi rst or second day 
after birth.
• During and immediately after pregnancy, 
paracetamol (acetaminophen) is the safest nono-
pioid analgesic, and opioids other than codeine 
and pethidine are preferred.
• Nonsteroidal anti-infl ammatory drugs are valu-
able analgesics but should be reserved for use 
during the second trimester of pregnancy and 
must be avoided after 32 weeks’ gestation.
•  Use the following table to make an individual 
risk-benefi t-ratio for your patient before starting 
analgesia:

Chapter Title
243
Prescribing Medicines in Pregnancy, 4th edition 1999, and amendments. 
Australian Government. Department of Health and Aging. Th
 erapeutic 
Goods Administration. http://www.tga.gov.au/docs/html/medpreg.htm or 
http://www.tga.gov.au/DOCS/HTML/mip/medicine.htm
Drugs in Pregnancy and Breastfeeding. http://www.perinatology.com/expo-
sures/druglist.htm
Th
 erapeutic Guidelines. http://www.tg.com.au
National Institutes of Health. US National Library of Medicine. Drugs 
and Lactation Database (LactMed). http://toxnet.nlm.nih.gov/cgi-bin/sis/
htmlgen?LACT
ObFocus. High risk pregnancy directory. http://www.obfocus.com/resources/
medications.htm
References
[1]  American Academy of Pediatrics Committee on Drugs. Th
  e transfer of 
drugs and other chemicals into human milk. Pediatrics 2001;108:776–
89.
[2]  McDonnell NJ, Keating ML, Muchatuta NA, Pavy TJ, Paech MJ. Anal-
gesia after caesarean delivery. Anaesth Intensive Care 2009;37:539–51.
[3]  Rathmell JP, Viscomi CM, Ashburn MA. Management of nonobstetric 
pain during pregnancy and lactation. Anesth Analg 1997;85:1074–87.
[4]  Roche S, Hughes EW. Pain problems associated with pregnancy and 
their management. Pain Reviews 1999;6:239–61.
Websites
Acute Pain Management: Scientifi c Evidence. Chapter 10.2. Th
 e pregnant 
patient. Second edition 2005, Dec 2007 update. Australian and New Zealand 
College of Anaesthetists and Faculty of Pain Medicine. Approved by Austra-
lian Government and National Health and Medical Research Council. http://
www.anzca.edu.au/resources/books-and-publications
Drug
Recommendation during Pregnancy
Recommendation during Breastfeeding
Paracetamol (acet-
aminophen)
Compatible throughout
Compatible
Aspirin
Avoid at conception and avoid chronic high doses dur-
ing pregnancy
Potential toxicity
Indomethacin
Avoid at conception, during fi rst 10 weeks of gestation, 
and after 32 weeks of gestation
Probably compatible
Diclofenac
Avoid at conception, during fi rst 10 weeks of gestation, 
and after 32 weeks of gestation
Compatible
Ibuprofen
As indomethacin
Compatible
Naproxen As 
indomethacin
Compatible
Ketoprofen As 
indomethacin
Compatible
Ketorolac As 
indomethacin
Compatible
Celecoxib
As indomethacin
Limited data, potential toxicity
Tramadol
Probably avoid in the fi rst trimester, but thereafter low 
risk (neonatal abstinence syndrome is possible)
Morphine
Compatible, but possible neonatal depression at birth 
and abstinence syndrome with third-trimester use
Probably compatible
Codeine 
As morphine, but less eff ective
Probably compatible
Pethidine (meperidine)
As morphine, but use alternative opioids if possible
Compatible, but use alternative opioids
Methadone
As morphine
Probably compatible
Oxycodone
As morphine
Probably compatible
Fentanyl
As morphine
Amitriptyline
Low risk throughout
Limited data, potential toxicity
Carbamazepine 
Compatible if used for epilepsy, but preferably avoid 
(risk of malformations)
Compatible
Gabapentin
Limited evidence suggests low risk
No data—probably compatible
Pregabalin
Insuffi
  cient data
No data—probably compatible
Ketamine
Low risk throughout
Clonidine
Probably avoid in the fi rst trimester 
Probably compatible
Bupivacaine
Low risk throughout
Probably compatible
Ropivacaine
Compatible throughout
Probably compatible
Lidocaine (lignocaine)
Compatible
Probably compatible

245
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 32
Pain in Sickle Cell Disease
Paula Tanabe and Knox H. Todds
Case report
Ruben is a 25-year-old male with sickle cell disease who 
presents for evaluation of moderate, constant right hip 
pain (rated as 6/10) and intermittent episodes of severe 
pain, reported as “crisis pain.” Ruben describes these cri-
ses as severe, occurring monthly, and feeling “as if all my 
bones are breaking.” Th
  e pain is most often experienced 
in his legs.
How often do individuals with 
sickle cell disease have pain?
Th
  is case depicts a typical scenario faced by therapists 
around the globe. Often, the pain associated with sickle 
cell disease (SCD) is poorly understood. Persons with 
SCD often experience both acute and chronic pain. It 
is now clear that more than half of patients with SCD 
report some type of pain on a daily basis. “Crisis pain,” 
the most severe pain experienced by persons with SCD, 
has been reported on up to 13% of all days. Crisis pain 
(acute pain) has been described as “if all my bones are 
breaking” or “being hit with a board.”
Th
 ese lifelong episodes have an abrupt onset, 
are episodic and unpredictable, and are associated with 
very severe pain. Individuals are usually not able to con-
duct normal activities during a painful crisis, which may 
last for several hours and up to a week or more.
Th
  e severity and frequency of pain crises var-
ies with the specifi c genotype. Patients with SS and SB0 
typically have more severe pain episodes when com-
pared with patients with SC and SB+. Th
  is is not to say 
that patients with SC and SB+ cannot experience pain-
ful episodes—the episodes are just more uncommon 
and infrequent.
Both physiological and psychological factors 
can trigger a painful crisis. Common triggers of painful 
crises include infection, temperature changes, and any 
type of physical or emotional stress. Common causes of 
acute pain include:
•  Hand-foot syndrome in children (dactylitis)
•  Painful crises: vasoocclusion
• Splenic sequestration
•  Acute chest syndrome
• Cholelithiasis
• Priapism
In addition to experiencing acute painful crisis, 
persons with SCD also often experience chronic pain. 
Specifi c causes of chronic pain include:
• Arthritis
• Arthropathy
•  Avascular necrosis (often in the hips and shoul-
ders and more common in persons with SC geno-
type)
• Leg ulcers
•  Vertebral body collapse
                                                              

246
Paula Tanabe and Knox H. Todd
How can pain be managed 
pharmacologically?
Th
 erapists must consider the need for chronic pain 
management as well as rescue medication for acute 
painful crises. Persons with more than three painful 
crises per year are candidates for hydroxyurea thera-
py, which has been shown to signifi cantly decrease the 
number of painful crises, as well as the incidence of 
acute chest syndrome.
General recommendations include:
•  Treat pain as an emergency
•  Assess pain levels frequently
•  Assess hydration status and maintain adequate 
hydration
•  Investigate other possible causes of pain/compli-
cations of the disease (acute chest syndrome, pri-
apism, splenic sequestration, cholelithiasis)
•  Do not withhold opioids when pain is severe
Analgesics for mild to moderate pain include 
acetaminophen (avoid if liver disease is present) and 
nonsteroidal anti-infl ammatory drugs (NSAIDs) such as 
ibuprofen or ketorolac (contraindicated in patients with 
gastritis/ulcers and renal failure: monitor renal function 
if used chronically).
Moderate to severe pain should be treated with 
opioids such as morphine sulfate or hydromorphone. 
Many patients with SCD-associated chronic pain may 
require daily doses of opioids to maintain optimal func-
tion. High doses of opioids are often necessary to treat 
painful crises. Meperidine is NOT recommended, since 
it may be associated with seizures and renal toxicity. Ac-
etaminophen or NSAIDs in combination with opioids 
may be helpful in treating severe pain crises.
Should I be concerned                
about the risk of addiction                
if prescribing opioids?
Opiophobia, the fear of prescribing opioids, is a world-
wide phenomenon. And certain pain syndromes remain 
poor indications for opioids (e.g., chronic back pain, 
headache). But SCD seems to have a good indication for 
opioids, and there are no data to suggest persons with 
SCD are at an increased risk of becoming addicted to 
opioids. Th
 e unjustifi ed fear of causing addiction results 
in undertreatment of the severe and debilitating eff ect 
of SCD pain. Pain in SCD should, therefore, always be 
aggressively treated. Behaviors often thought of as being 
suspicious for addiction are frequently an indication of 
undertreatment of pain or disease progression (called 
“pseudo-addiction”).
Are there any nonpharmacological 
therapies for chronic and acute 
pain episodes?
Many therapies have been reported by persons with 
SCD as helping either avoid painful crises or treat 
chronic pain. Th
  ese are listed below:
•  Maintaining adequate hydration
•  “Journaling” or keeping a diary of diet, activities, 
and stressors, which helps to identify triggers of 
painful crises
•  Heat and massage
•  Use of a variety of herbs and vitamins (in particu-
lar, folic acid)
•  Careful attention to a healthy diet (high quanti-
ties of fruits and vegetables, low amounts of pro-
tein).
What complications may be 
important to recognize other than a 
pain crisis?
Sickle cell disease is associated with early mortality in 
many countries, although accurate life expectancy esti-
mation is not available. Historically, children with SCD 
would not survive into adulthood. However, due to the 
use of prophylactic penicillin until age fi ve to prevent 
sepsis, children are surviving, and many adults in the 
United States are living well into their 60s. Th
 e follow-
ing is a list of serious complications that should always 
be considered when treating a person with SCD. Th
 ese 
complications are more common in childhood; howev-
er, they can also occur in adults:
• Chronic anemia
•  Acute splenic sequestration
• Sepsis
• Aplastic crisis
•  Acute chest syndrome
• Stroke
Chronic complications common in adults include:
• Pulmonary hypertension
•  Progressive renal disease
• Chronic anemia
• Retinopathy

Pain in Sickle Cell Disease
247
•  Gallbladder, liver, and lung infarction
•  Iron overload (if the patient has received numer-
ous blood transfusions)
• Depression
What is the pathophysiological 
mechanism of sickle cell disease?
Pain crises are triggered by deoxygenation and by the 
resulting polymerization of the hemoglobin. A triad of 
ischemia, infarction, and infl ammation contribute to the 
pathophysiology of pain. Mechanisms include damage 
to the vascular endothelium and chemical mediators of 
infl ammation, microinfarctions caused by local capillary 
sickling, ischemia, somatic symptoms (muscles, ten-
dons, ligaments, bone, and joints), and visceral symp-
toms (spleen, liver, and lungs), often described by the 
patient as being vague, diff use and/or dull pain.
Tips from a complementary 
medicine specialist
Many complementary alternative medicine strategies 
have been found to both limit the frequency of pain 
crises and improve patients’ quality of life. Careful at-
tention to nutrition, obtaining adequate sleep, the use 
of heat, and massage have all been reported by persons 
with SCD who function at a very high level. Use of com-
plementary strategies should therefore be encouraged.
Pearls of wisdom
•  Many persons with SCD experience pain on a 
daily basis.
•  Individuals with SCD often experience both acute 
and chronic pain.
•  Pain episodes begin in childhood and continue 
throughout the lifespan.
•  Acetaminophen and NSAIDs are helpful in man-
aging mild and moderate pain.
•  Opioids are often required to manage acute pain-
ful crises.
•  Some patients will require chronic use of opioids 
on a daily basis to manage pain and improve daily 
function.
•  Complementary strategies such as the use of 
heat, suffi
  cient sleep, hydration, massage, and ex-
cellent nutrition are reported as being helpful.
•  Again, opioids are very eff ective and should not 
be withhold from a patient suff ering from sickle 
cell disease.
References
[1]  National Institutes of Health. National Heart, Lung, and Blood Insti-
tute. Th
  e management of sickle cell disease, 4th ed. NIH publication no. 
02–2117. Washington, DC: National Institutes of Health; 2002. 
[2]  Smith WR, Penberthy LT, Bonbjerg VE, McClish DK, Roberts JD, Dah-
man B, Aisiku IP, Levenson JL, Roseff  SD. Daily assessment of pain in 
adults with sickle cell disease. Ann Intern Med 2008;15:94–101.
Websites
http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_WhatIs.html
http://www.nhlbi.nih.gov/health/prof/blood/sickle/
http://consensus.nih.gov/2008/2008SickleCellDRAFTstatementhtml.htm

249
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
Andreas Schwarzer and Christoph Maier
Chapter 33
Complex Regional Pain Syndrome
In 1865, the neurologist Silas Weir Mitchell reported 
about soldiers complaining of strong burning pain, pro-
nounced hyperesthesia, edema, and reduction of motor 
function of the limb following injuries of the upper or 
lower extremity. Mitchell named these disturbances “cau-
salgia.” In the following years, these symptoms were de-
scribed again and again after extremity injuries but were 
labeled diff erently (algodystrophy, refl ex sympathetic dys-
trophy, Morbus Sudeck). Currently, this disease pattern is 
referred to as complex regional pain syndrome (CRPS). 
Two types are recognized: CRPS type I without nerve in-
jury and CRPS type II associated with major nerve injury.
What are the main characteristics 
of patients with CRPS?
As a general rule, the symptoms of CRPS manifest 
themselves in the distal extremity (usually in the upper 
limb, and less often in the lower limb). Almost all pa-
tients (90–95%) suff er from pain, which is described as 
burning and drilling and is felt deep in the tissue. Fur-
thermore, an edema of the aff ected extremity, with an 
emphasis on the dorsal areas (dorsum of the hand or 
foot) can be observed in almost all patients. Pain and 
edema increase when the limb is hanging down. Further 
essential disease features are the following: (1) patients 
suff er from sensory, motor, and autonomic impairment; 
(2) the symptoms spread beyond the area of the primary 
damage and cannot be assigned to the supply area of one 
single nerve, e.g., the whole hand is aff ected  following 
fracture of the radius; (3) usually both joints and nerves 
are aff ected; (4) patients often present with psychological 
disturbances. Th
  ere are no clinical diff erences  between 
CRPS type I and type II; except for the nerve damage.
What is the incidence of CRPS, and 
are there specifi c triggers?
CRPS is a rare disease. Approximately 1% of patients de-
velop CRPS following a fracture or nerve injury. How-
ever, exact data on prevalence do not exist. In a current 
study from the Netherlands, the incidence was esti-
mated 26/100,000 persons per year, with females being 
aff ected at least three times more often than males. In 
another population-based study from the United States, 
the incidence was estimated at 5.5/100,000 persons per 
year. Th
  e upper extremity is more often aff ected, and a 
fracture is the most common trigger (60%).
What is the explanation for 
development of CRPS?
In almost all of the patients (90–95%) there is an ini-
tiating noxious event (trauma) in the clinical history. 
Th
  e reason why only some patients develop CRPS is 
still unclear. Th
 ere is also no comprehensive theory 
that can explain the diversity and the heterogeneity 
of the symptoms (edema, central nervous symptoms, 

250
Andreas Schwarzer and Christoph Maier
joint involvement, etc.). Current attempts explain sin-
gle symptoms, but not the overall picture. An essential 
hypothesis about the main pathomechanism for de-
veloping CRPS includes infl ammatory  processes.  Th
 is 
point of view is supported by the fact that the classic 
infl ammatory signs (edema, redness, hyperthermia, 
and impaired function) are prominent, especially in the 
early stages of the disease, and that these symptoms are 
positively infl uenced by the use of corticosteroids.
What is the prognosis of patients 
who have developed CRPS?
Th
  e number of favorable cases that heal up spontane-
ously or following adequate treatment (and avoidance 
of mistreatment), are unknown. Prognosis regarding the 
full recovery of function of the aff ected limb is unfavor-
able, and only 25–30% of all patients fully recover, ac-
cording to the degree of severity and their comorbidity. 
Th
  e extent of the eff ects of osteoporotic changes on the 
prognosis is still unclear. Th
  e following symptoms point 
to an unfavorable course of the disease: a tendency to 
stiff  joints, contracture in the early stages, pronounced 
motor symptoms (dystonia, tremor, and spasticity), ede-
ma, and psychological comorbidity.
Which treatment strategies play an 
important role in the management 
of CRPS?
Treatment should take place in three steps: in the begin-
ning, treatment of pain at rest and treatment of edema 
have utmost priority. Next to pharmacological treat-
ment, rest and immobilization are most important. In 
the second stage, the therapy should include treatment 
of the pain during movement as well as during physi-
cal and occupational therapy. Pain treatment takes a 
back seat in the third stage, when the emphasis is on 
the treatment of functional orthopedic disorders as well 
as on psychosocial reintegration. Th
 e intensifi cation  of 
physical therapy can be limited due to reoccurrence of 
pain or edema. Th
  e main rule is that the treatment must 
not cause any pain.
Case report
Etta, a 58-year-old offi
  ce worker, had bad luck when 
she left her house on a rainy day and fell on the slip-
pery steps of her front porch. A fracture of the left distal 
radius was diagnosed in the hospital. Everything seemed 
fi ne after the fracture was treated by osteosynthesis and 
cast, but within a few days after discharge she felt an in-
creasing constant burning pain in her forearm, and her 
fi ngers got swollen. When visiting her surgeon, she com-
plained about the pain, and the cast was removed.